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The genus Peucedanum traditional Uses, phytochemistry and Pharmacological Properties: A Review Parisa Sarkhail

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S0378-8741(14)00628-X http://dx.doi.org/10.1016/j.jep.2014.08.034 JEP8996

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Journal of Ethnopharmacology

Received date: 23 April 2014 Revised date: 25 August 2014 Accepted date: 25 August 2014ds Cite this article as: Parisa Sarkhail, The genus Peucedanum traditional Uses, phytochemistry and Pharmacological Properties: A Review, Journal of Ethnopharmacology, http://dx.doi.org/10.1016/j.jep.2014.08.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The Genus Peucedanum Traditional Uses, Phytochemistry and Pharmacological Properties: A Review Parisa Sarkhail Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 14176, Iran. Correspondence Dr. Parisa Sarkhail, Assistant professor of Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 16th Azar St. Tehran, Iran, PO Box 141556451,Tel/Fax +98 21 64122326, Email: [email protected]

Abstract: Ethnopharmacological relevance: The genus Peucedanum (Apiaceae) comprising more than 120 species are widely distributed in Europe, Asia and Africa. The ethnopharmacologial history of this genus indicated that some extracts of aerial and underground parts of several Peucedanum species have used in folk medicine for treatment of various conditions, such as cough, cramps, pain, rheumatism, asthma and angina. Aim of the review: This review focuses on ethnopharmacological uses of Peucedanum species, as well as the phytochemical, pharmacological and toxicological studies on this genus. Through this review, we intend to highlight the known and potential effects of the Peucedanum species or their isolated compounds and show which of traditional medicine uses have supported by pharmacological investigations. Methods: Information on the Peucedanum species collected from scientific journals, books, thesis and reports via a library and electronic search (using Google Scholar, Pubmed, Scopus, Web of Science and ScienceDirect). This review covers the available literature from 1970 to the end of September 2013.

Results: Although, there are about 120 species in this genus, so far many species that have received no or little attention and the most of pharmacological studies were performed just about 20 species. Many phytochemical investigations on this genus confirmed Peucedanum species are rich in essential oils and coumarins. The present review article shows Peucedanum species have a wide spectrum of pharmacological activities that the most reported activities of Peucedanum plants come back to the presence of coumarins, flavonoids, phenolics and essential oils Conclusions: The present review confirmed some Peucedanum species have emerged as a good source of the traditional medicine for treatment of inflammation, microbial infections, cardiopulmonary diseases and provides new insights for further investigations on isolated compounds specially on praeruptorins to find novel therapeutics and drug discovery. However, for uses of Peucedanum species to prevent and treat various diseases the additional pharmacological studies to find the mechanism of action, safety and efficacy of them before starting clinical trials are required.

Keywords:

Peucedanum;

Apiaceae;

Traditional

uses,

Phytochemicals;

Pharmacological effects, Coumarins.

Some chemical compounds studied in this review article Bergapten (CID: 2355); Columbianadin (CID: 6436246); Imperatorin (CID: 10212); Isosamidin (CID: 442133); (+)-trans-kellactone (CID 11436940); Osthole (CID: 10228); Osthrutin (CID: 5281420); Ostruthol (CID: 6441273); Peucedanin (CID: 8616); Praeruptorin A (CID: 38347607); (−)-Praeruptorin A (CID: 38347601); (+)Praeruptorin A or Praeruptorin C (CID: 5320691); Praeruptorin B (CID: 5319259);

(+)-Praeruptorin B or Praeruptorin D (CID: 25717254); Praeruptorin E (CID: 6440581); Pteryxin (CID: 5281425); Visamminol (CID: 5315249); Xanthotoxin (CID: 4114).

1. Introduction The genus Peucedanum, (Apiaceae) is a large group comprising more than 120 species that are widely distributed in Europe, Asia, Africa and North America (Ciesla et al., 2009; Skalicka-Wozniak et al., 2009a,b). The ethnopharmacological history of Peucedanum indicates that some species have been used in local medicine to treat various conditions, including sore throat, coughs, colds, headaches (Hisamoto et al., 2003; Morioka et al., 2004) asthma, angina (Schillaci et al., 2003), cramps, epilepsy, gastrointestinal disorders, rheumatism, gout, and cardiovascular problems, and as a chemopreventive agent (Leporatti and Ivancheva, 2003) and antifebrile (Ikeshiro et al., 1992). Because of their versatile therapeutic traditional uses, a number of phytochemical investigations have been carried out on Peucedanum plants. To date, comparative phytochemical data are available for nearly 50 Peucedanum species. Several bioactive substances, including coumarins, polyphenols, amines, glycosides, flavonoids, phenolic acids, essential oils, diterpenes and other components, have been isolated from different species of Peucedanum (Fraternale et al., 2000; Hisamoto et al., 2003; Shults et al., 2003; Kapetanos et al., 2008). Coumarins and essential oils are considered the main constituents in nearly all Peucedanum plants and can be responsible for many of their biological and pharmacological activities of Peucedanum species (Ciesla et al., 2009; SkalickaWozniak et al., 2009a and 2009b).

According to the Chinese Pharmacopoeia (2010 Edition), some species, such as P. praeruptorum and P. japonicum, are highly valued plants because of their pharmacological activities against cancer (Shen et al., 2012), microbes (Yang et al., 2009), diabetes (Nukitrangsan et al., 2012), obesity (Okabe et al., 2011), and reactive oxygen species (Hisamoto et al., 2003). The most important pharmacological properties,

including

calcium

antagonist

activity

(Chang

et

al.,

1994a);

neuroprotection (Yang et al., 2013); anti-asthma, vasorelaxant and antiallergic effects (Aida et al., 1998; Zhao et al., 1999); cardiopulmonary protection (Chang et al., 1994b; Zaho et al., 1999; Wang et al., 2004); hepatoprotection (Song et al., 2011); anti-tumor activity (Mizuno et al., 1994; Liang et al., 2010; Ren et al., 2013); and anti-platelet aggregation activity (Aida et al., 1995), are related to the some khellactone coumarins (praeruptorins) that were identified for the first time in the roots of P. praeruptorum, P. japonicum and P. decursivum. Some praeruptorins have shown the strong anti-tumoral activity in various cell lines (Chang-yih et al., 1992; Chang et al., 2008, Liang et al., 2010). Recently, the structure-activity relationship of praeruptorin derivatives has been investigated to find more potent anti-tumor drugs (Fong et al., 2008; Shen et al., 2012). There are several studies about the pharmacokinetic profile of praeruptorins in human and rat liver microsomes (see the review by Sarkhail et al. (2013b)). The main metabolic pathways of praeruptorins in hepatic microsomes are oxidation, hydrolysis and acyl migration of the C-3’ and/or C-4’ position (Ruan et al., 2011; Jing et al., 2013). Other known and potential coumarins isolated from Peucedanum plants, for example xanthotoxin, psoralen, and bergapten, have been reported to possess antiplatelet aggregation (Chen et al., 2008) and monoamino-oxidase inhibition activity (Huong et al., 1999). In addition, some of these furanocoumarins are phototoxic in

irradiation (Ojala et al., 1999). A number of phenolic acid and flavonoid compounds are the main compounds responsible for anti-tyrosinase and radical scavenging activity (Sarkhail et al., 2013; Hisamoto et al., 2003). Kuzmanov et al. (1981) used coumarin and flavonoid compounds for chemotaxonomic analysis of six species native to Bulgaria. Furthermore, the study of the essential oil composition of various species of this genus seems valuable for chemotaxonomic classification and for differentiating the individual species with unclear anatomic and morphological structures. The volatile oils of different parts of Peucedanum species usually consist of monoterpenes and sesquiterpene hydrocarbons, oxygenated sesquiterpenes, aliphatic alcohols and esters (Fraternale et al. 2000; Skalicka-Woźniak et al., 2008). The effectiveness of some secondary metabolites or extracts of various Peucedanum plants has been evaluated and supported by pharmacological studies (Aida et al., 1998, Hiermann and Schant, 1998; Skalicka-Woźniak et al., 2010). However, more investigations in vitro, in vivo and in clinical trials are required to determine their safe doses and adverse effects (toxicity) for therapeutic uses. The present review focuses on ethnopharmacological uses of Peucedanum species, as well as the phytochemical, pharmacological and toxicological studies of this genus. It includes many published pharmacological data, not only supporting some local medicine uses but also exposing the lost links between traditional knowledge and new information about Peucedanum plants. This review highlights the importance of some coumarins, such as praeruptorins A and B, for preventing or treating cancer, cardiovascular problems and some inflammatory diseases. All these data warrant further research on Peucedanum species to find the mechanisms behind their pharmacological properties and to identify new potential therapeutic applications and drug discovery.

2. Taxonomy Peucedanum L. (fam. Apiaceae subfamily. Apioideae trib. Peucedaneae) is a large, heterogeneous and polyphyletic genus of more than 120 species distributed in Europe, Asia, Africa and North America. Because of the high degree of heteromorphy, the taxonomic value of the genus Peucedanum exposes problems, and it has been partly revised (Pimenov and Leonov 1993). Many species (711 plants) are reported as belonging to the Peucedanum genus, but only 69 species correspond to an accepted scientific name, and others are synonyms or unresolved names (The Plant List 2013). Of the species are listed in this article (see Table 1), thirty-seven of them, including P. alsaticum, P. arenarium, P. austriacum, P. carvifolia, P. cervaria, P. cervariifolium, P. coriaceum, P. delavayi, P. dissolutum, P. formosanum, P. harrysmithii var. subglabrum, P. japonicum, P. lancifolium, P. ledebourielloides, P. longifolium, P. longshengense, P. morisonii, P. obtusifolium, P. officinale, P. oligophyllum, P. oreoselinum, P. ostruthium, P. palustre, P. paniculatum, P. praeruptorum, P. rubricaule, P. ruthenicum, P. schotti, P. tauricum, P. terebinthaceum, P. turgeniifolium, P. verticillare, P. vittijugum, P. vourinense, P. wawrii, P. wulongense and P. zenkeri have been confirmed as accepted scientific names. The last taxonomic revision of this genus showed that many genera, such as Cervaria, Holandrea, Imperatoria, Oreoselinum, Pteroselinum, Thysselinum, Tommasinia and Xanthoselinum, separated from Peucedanum. For example, P. ostruthium and P. oreoselinum referred to Imperatoria and Oreoselinum, respectively (Spalik et al. 2004). Traditionally, fruit characters, both external features and anatomical features, have used for classification of the family Apiaceae. However, fruit characters of many of Peucedanum species have not been supported by recent molecular phylogenetic

investigations. Peucedanum spp. are traditionally identified by flattened orthospermus fruits with more and less developed lateral wings, a broad commissure and the lack of prominent dorsal ribs. Because of the great diversity of life forms, leaf and fruit structures, and chemical components, this genus has dissimilar character patterns that showed a poor relationship with morphology and were difficult to use for taxonomy (Drude, 1897-98). For example, the boundaries between Peucedanum and Angelica are not clear, and two genera are distinguished from each by commissure width of fruits (Ostroumova and Pimenov 1997; Theobald 1971). However, this character seems not to be useful for some plants, e.g., A. decursiva, with a quite large commissure, can be referred to as Peucedanum, whereas recent taxonomic revision by Liu et al. (2006) showed that P. decursivum belongs to genus Angelica not Peucedanum. The taxonomy of the polymorphous genus Peucedanum has been revised by several techniques, including comparative phytochemical data, immunochemical investigations and sequencing of the internal transcribed spacer of nuclear rDNA (ITS rDNA) (Spalik et al. 2004). For instance, Hadacek & Samuel (1994) compared the composition of secondary metabolite of 13 collected Peucedanum species from central Europe, using high performance liquid chromatography (HPLC) method with ultraviolet-visible (UV) diode array detection. They found that peucedanin, a linear furanocoumarin, is a major compound in HPLC profiles of P. coriaceum, P. gabrielae, P. vourinense and P. officinale and can be used as a chemotaxonomic marker. Kuzmanov et al. (1981) used coumarin and flavonoid compounds for chemotaxonomic analysis of six native Bulgarian species (P. officinale, P. longifolium, P. ruthenicum, P. vittijugum, P. cervifolia and P. oligophyllum) of two Peucedanum sections, sec. Peucedanum and sec. Palimbioidea. All species of these

two sections were similar in their flavonoid content. Peucedanum officinale, P. longifolium and P. ruthenicum, but not P. vittijugum, belonging to sec. Peucedanum, were rich in coumarins, while P. cervifolia and P. oligophyllum from sec. Palimbioidea were poor species of coumarins. These findings show that coumarins are valuable chemotaxonomic markers for classification of the genus Peucedanum and that P. vittijugum can be separated into a new section because of dissimilar coumarin content. Recently, some taxonomic revisions indicated that many Peucedanum species should be transferred to other genera based on morphological, anatomical and molecular evidence. Recent re-classification of several African species of Peucedanum showed that these plants completely separate from the superficially similar Eurasian species. For instance, P. galbanum was reassigned to the Notobubon genus because it shares the additional rib vittae of N. galbanum fruits and other characters (Winter et al., 2008). This review article discusses the various arguments for and against splitting Peucedanum into more segregates. Although the names of several plants in this review article have not been accepted by The Plant List database (2013), I decided to use the names reported by the authors in their original works and show their taxonomic validation (scientific names, status and synonyms) in Table 1.

3. Ethnobotanical uses of Peucedanum species

A review of books and papers shows that several Peucedanum species are used in local medicine in some Asian and European countries. Although pharmacological investigations of Peucedanum species used in local medicine are not extensive, some studies have identified potential health effects. For example, in the

Canon of Medicine, one of the most famous traditional medicine books belonging to a Persian scientist named Ibn-Sina (Avicenna), P. grande was considered a beneficial diuretic herb for destructing, expelling, and preventing kidney calculi (Ibn e Sina, 1920; Faridi et al., 2012). Recently, Aslam et al. (2012a,b) confirmed the nephroprotective action of P. grande fruits against cadmium and mercuric chloride nephrotoxicity. In Central European local medicine, essential oil fruits of P. alsaticum and P. cervaria are used as an expectorant, diaphoretic, diuretic, stomachic, sedative, and antimicrobial agent (Skalicka-Woźniak et al., 2010). Peucedanum galbanum traditionally is used in Africa to treat various ailments, including vesical catarrh, kidney and bladder ailments, prostate problems, swelling of glands and retention of urine and as an abortifacient (Campbell et al., 1994). In Austrian traditional medicine, rhizomes of P. ostruthium have a long history of treatment of inflammatory diseases (Joa et al., 2011). Peucedanum ostruthium was a valuable plant in 19th-century medical science, and some synonyms have been reported for it such as Imperatoria ostruthium, Selinum ostruthium and Angelica officinalis (see Table 1). The alcohol extract of its rhizome (Radix imperatoriae), named Remedium divinum hoffmannii, has been applied as a diuretic for chronic indigestion, a stimulant, a stomachicum, as well as for healing typhoid, intermittent fever, paralytic conditions, and in delirium treatments. Externally, it was applied as a powder for ulcers and cancer (Butenandt and Marten, 1932; Gökay et al., 2010). In Iranian local medicine, the aerial parts of P. pastinacifolium are commonly used as an antihyperlipidemic vegetable (Movahedian et al., 2009). In Indian local medicine, the essential oil and distilled water of P. graveolens (a synonym for Anethum graveolens L.) fruits are used to relieve flatulence, hiccup, colic and abdominal pain in children and in adults (Roy and Urooj, 2012).

The most frequently employed and investigated Peucedanum species are P. praeruptorum, P. japonicum and P. decursivum. The dried root of P. praeruptorum, Baihua qianhu, has been one of the most popular herbs in traditional Chinese medicine (TCM) for more than 1500 years and is officially listed in the Chinese Pharmacopoeia (Editorial Committee of Chinese Bencao, 1998; China Pharmacopoeia Committee, 1999). In TCM, Qian-Hu, including the roots of two species of P. praeruptorum and P. decursivum, is used for treatment of some respiratory diseases and pulmonary hypertension (Zhao et al., 1999). At present, it is possible to suggest the root and/or rhizome of P. praeruptorum for the following: (i) to treat respiratory diseases, pulmonary hypertension (Zhao et al., 1999; Wu et al., 2003, He et al., 2007), and chest pain, presumably including angina pectoris (Rao et al., 1988); (ii) to treat symptomatic coughs and dyspnea and as an antitussive and mucolytic agent; and (iii) as an antiseptic in upper respiratory infections (Chang et al., 2001; He et al., 2007; Song et al., 2011; Liang et al., 2012). A number of species from Peucedanum are used for the treatment of asthma, sore throat and angina and cardiovascular problems (Rauwald et al., 1994; Chen et al., 2008; Skalicka-Wozniak et al., 2010). For instance, P. japonicum roots are still prescribed against coughs, colds, headaches and antifebrile in Japan and sometimes are applied as a ginseng substitute (Ikeshiro et al., 1992). The root of P. formosanum, known as “Taiwan Qian-Hu”, has been traditionally used for treating coughs, fever, headache and excessive sputum caused by colds (Chen et al., 2008). The root and fruit decoction of P. officinale can be used as a cardio-tonic, astringent and emmenagogue (Leporatti and Ivancheva, 2003). In Table 2, the traditional uses and local names of twelve Peucedanum species from different countries are summarized. However, the reported data in papers

and books have no local medicine information regarding most species of Peucedanum.

4. Phytochemicals

Like all plants belonging to the Apiaceae family, species of Peucedanum are rich in coumarins and essential oils. In addition, some phenolic acids, flavonoids, terpenoids and other components have been identified in this genus. Thus far, more than 300 molecules have been identified from Peucedanum. The chemical composition of some species, such as P. knappii (Sarkhail et al., 2013a) and P. formosanum (Chen et al., 2008), are inadequately known, although few flavonoids or coumarins have been detected in these plants. A total of 158 coumarins, 13 phenolic acids, 13 flavonoids, 11 phenylpropanoids, 8 chromones, 9 fatty acids, 2 steroids, and a number of volatile oils (monoterpenoids, sesquiterpenoids) have been identified from Peucedanum species. Phytochemical analysis of the essential oils from Peucedanum species summarized in Table 3, and coumarins, flavonoids, phenolics and other components are reviewed in Table 4. 4.1. Terpenoids Terpenoids are classified according to the number of isoprene units. For example, monoterpenoids (C10) are made from two isoprene units, sesquiterpenoids (C15) from three units, diterpenoids (C20) from four units, and triterpenoids (C30) from six units (Huang et al., 2012). Monoterpenoids and sesquiterpenoids are the primary compounds of the essential oils that are mainly extracted by hydrodistillation (HD), steam-distillation (SD), headspace solid-phase microextraction techniques (HSSPME) and supercritical methods, and then identified by gas chromatography (GC)based techniques (Sides et al., 2000; Skalicka-Wozniak et al., 2009a).

The genus Peucedanum is rich in aromatic plants, but taxonomically, many of its species are still unresolved. Because characterization of each Peucedanum species by anatomical and morphological features is difficult, chemical analysis of essential oils has played an important role in identifying chemotaxonomic markers. Analysis of essential oils indicated that the main components of Peucedanum species oils are monoterpene hydrocarbons (Kapetanos et al., 2008; Figuérédo et al., 2009), and in many Peucedanum species including P. officinale, P. alsaticum, P. austriacum, P. oreoselinum, P. longifolium and P. cervaria, (±)-α-pinene (4.0% to 38.7%) (Kapetanos et al., 2008; Skalicka-Wozniak et al., 2008b and 2009a) is the major component of essential oils. However, some species, such as P. ruthenicum (Alavi et al., 2006a) and P. paniculatum (Vellutini et al., 2005), are dominated by other monoterpenes or sesquiterpenes (Tepe et al., 2011). Climatic factors variations, extraction techniques and different plant parts could influence the quality and quantity of essential oil compounds. For example, in the fruit essential oil of P. oreoselinum, the amounts of the two main components γ-terpinene (12.2% to 17.5%) and β-pinene (8.5% to 14.5%) increase in the presence of sunlight. Limonene is the major compound (44.1% to 82.4%), and α-pinene is found in all studied P. oreoselinum samples at concentrations of approximately 4.0% to 11% (Motskute and Nivinskene, 1999). Skalicka-Wozniak et al. (2009a) studied the effects of different extraction methods on the essential oils from P. cervaria fruits. In both HD and HS-SPME extracts, α-pinene and sabinene were the dominant compounds (31.3% to 38.6%), but the amounts of these monoterpenes were larger than those isolated by HD. In contrast, α-terpinene, β-linalool, trans-verbenol, β-bourbonene and α-humulene were only detected by HD. In that study, more than 80% of oil from P. cervaria included α-

pinene, sabinene, and β-pinene, confirming the close botanical relationship of P. cervaria with P. alsaticum, P. schotti, P. scoparium, P. oreoselinum and P. petiolare. Analysis of the essential oil of P. officinale showed the flower oil differs from the other parts of plant by its significant quantity of α-phellandrene (Figuérédo et al., 2009). In P. ruthenicum the dominant compounds from leaf, flower and fruit oils are not similar. In leaf oil, thymol (18.3%) and β-bisabolene (13.3%) are the major components, while these compounds are not found in flowers and fruits of P. ruthenicum (Alavi et al., 2006b). In another study, higher humidity changed the amounts of thymol and β-bisabolene of leaf oil from P. ruthenicum to 57.8% and 6.0%, respectively (Alavi et al., 2006a). The volatile oils of different parts of P. petiolare were analyzed by Mirza et al. (2005). They showed that α-pinene (42.6% to 47.3%) and sabinene (42.3% to 45.9%) are the major components of leaf and seed oil, whereas in the rhizome oil, sesquiterpenes (51%), β-bisabolene (31.3%), and (E)sesquilavandulol (20.5%) are the main components. β-Bisabolene and (E)sesquilavandulol are only found in large amounts in the rhizome of P. petiolare (Mirza et al., 2005), and β-bisabolene is detected in a high quantity (13.29%) in the leaf oil of P. ruthenicum (Alavi et al., 2006b). P. alsaticum, P. cervaria (SkalickaWozniak et al., 2008b; Chizzola, 2012), P. verticillare, P. ostruthium, P. petiolare (Mirza et al., 2005) and P. ruthenicum (Alavi et al., 2006b) contain a large quantity of sabinene. Cisowski et al. (2001) reported that the major components of essential oil from rhizome of P. ostruthium are monoterpenes, sabinene (35.2%) and 4-terpineol (26.6%), while sesquiterpenes, β-caryophyllene (16.1%) and α-humulene (15.8%) are found in significant quantities in herb volatile oil. P. galbanum (Campbell et al., 1994), P. cervaria (Kapetanos et al., 2008) and P. ruthenicum (Alavi et al., 2006b)

oils contain significant amounts of p-cymene (38.7%, 7.7% and 6.21%, respectively), which is only present at small amounts in other Peucedanum species, such as P. petiolare and P. oreoselinum, P. alsaticum and P. officinale. In addition, three ρmenthatrienes, unique compounds belonging to Apium graveolens and Petroselinum crispum, as well as coumarins, xanthotoxin and psoralen, are found in P. galbanum oil (Campbell et al. 1994). Schmaus et al. (1989) analyzed the volatile oils of fruits, stalks, leaves, and roots of P. palustre. Monoterpene hydrocarbons are the main compounds in the fruit and stalk oils, while in the root oil monoterpene hydrocarbons (33%) and oxygenated sesquiterpenes (41%) are significant. Only in the oil of root has trans-sesquilavandulol been found in large amounts (37.2%). Because of the presence of similar primary sesquiterpenes, alcohols, trans-cyclobutyl sesquilavandulol and lancifolol (Figure 1), there is a close chemotaxonomic relationship between P. palustre and P. lancifolium oils (Schmaus et al., 1989). Fraternale et al. (2000) confirmed α-phellandrene (5.6% to 20.8%) is the one of the major compounds in P. verticillare oil. Limonene is not detected in this oil, whereas P. oreoselinum, P. grande, P. cachrydifolia, P. officinale, P. cervaria, P. alsaticum, P. longifolium, P. austriacum and P. zenkeri have a significant amount of (±)limonene. Moreover, the presence of some compounds distinguished P. verticillare oil from other Peucedanum species’ oil: (E)-anethole, which reaches approximately 30% in the oil, and epicamphor, which reaches approximately 7.8%, are not found in the essential oils from P. oreoselinum, P. officinale, P. grande, P. cachrydifolia and P. zenkeri (Fraternale et al., 2000). Approximately 3.5% of the oil extracted from the fresh fruit of P. verticillare is nerol, which is only detected in trace amounts of P. cachrydifolia oil. The essential oils of P. verticillare, P. palustre (Vuorela et al.,

1989), P. zenkeri (Menut et al., 1995), P. officinale and P. cervaria (Kapetanos et al., 2008) are rich in myrcene, a compound that occurs in small amounts in P. alsaticum, P. austriacum, P. oreoselinum, P. longifolium and P. cachrydifolia (Kapetanos et al., 2008). In conclusion, P. verticillare oil chemotaxonomically is characterized by the presence of anethole and epicamphor and the absence of limonene (Fraternale et al., 2000). Bornyl acetate, the main compound (81%) in the essential oil of P. officinale (Evergetis et al., 2012), is found only in P. scoparium (Masoudi et al, 2004) but not reported in other previous studies on P. officinale oils (Jaimand et al., 2006; Figuérédo et al., 2009). In 2001, Cisowski et al. analyzed the essential oil from P. ostruthium herb and rhizome. β-Caryophyllene (16.1%) and α-humulene (15.8%) are the dominant compounds in the herb oil, while sabinene (35.2%) and 4-terpineol (26.6%) are the major compounds in the rhizome oil. Moreover, a coumarin (osthole) is in both essential oils (5.5% in herb oil and 5.1% in rhizome oil) (Cisowski et al., 2001). In a few species of Peucedanum, such as the fruit oil of P. tauricum (Bartnik et al., 2002), there are high levels of sesquiterpenoids. Additionally, rhizome oil of P. petiolare, P. longifolium, P. cervariifolium and P. ruthenicum has a high level of sesquiterpenes. Several sesquiterpenes were isolated for the first time from the genus Peucedanum. For example, two new guaiane-type sesquiterpene hydrocarbons, guaia1(10),11-diene and guaia-9,11-diene (Figure 1), were isolated from the fruit oil of P. tauricum (Tesso et al., 2005). From the leaves and roots of P. paniculatum, essential oils were obtained by Vellutini et al. (2005). Eight novel, natural, irregular monoterpene esters were identified, and they have lavandulyl or cyclolavandulyl skeletons (see Figure 1). β-Cyclolavandulyl

acetate and isobutyrate (16.1% and 17.8%, respectively) are the major compounds in the leaf oil, whereas β-isocyclolavandulyl and β-cyclolavandulyl acetates (15.8% and 13.9%, respectively) are the main components of the root oil. For the first time, the βcyclolavandulyl

ester

compounds,

including

β-cyclolavandulyl

acetate,

β-

cyclolavandulyl isobutyrate, β-cyclolavandulyl isovalerate and β-isocyclolavandulyl acetate, and β-isocyclolavandulyl esters, such as β-isocyclolavandulyl acetate, βisocyclolavandulyl

propionate,

β-isocyclolavandulyl

isobutyrate

and

β-

isocyclolavandulyl isovalerate, were isolated from P. paniculatum leaf and root oils (Vellutini et al., 2005) (see Figure 1). The presence of trans-sesquilvanadulol is a characteristic of P. lancifolium and P. palustre oil and shows the close botanical relationship of two species because it is not detected in other Peucedanum plants (Kubeczka et al., 1989). A new acyclic diterpenoid, peucelinendiol (Figure 1), was identified for the first time in the ether extract of P. oreoselinum root by Lemmich (1979). Trace amounts (0.2%) of neophytadiene (linear diterpene) and abietatriene (cyclic diterpene) are found in essential oils of P. austriacum and P. longifolium, respectively (Kapetanos et al., 2008) (Figure 1). Tanshinone I (212) and tanshinone IIA (213) (see Figure 12) are two diterpene quinones in P. praeruptorum root extract (Zhang et al., 2005c). The most prevalent triterpenes in Peucedanum species are β-sitosterol (Kong et al.,1993; Huang et al., 2000; Xu and Kong, 2001; Yan et al., 2008;) and daucosterol (Xu and Kong, 2001; Yan et al., 2008; Zheng et al., 2010).

4.2. Coumarins Coumarins are a large class of plant secondary compounds found in the highest levels in the fruits, followed by the roots, stems and leaves. This group of natural compounds has received great attention because of their biological activities.

Coumarins have a benzopyrone skeleton. They include four major sub-types: simple coumarins, furanocoumarins, pyranocoumarins, and pyrone-substituted coumarins. Furanocoumarins consist of a five-membered furan ring fused with the coumarin nucleus and are divided into linear (psoralen type) or angular (angelicin type) forms with substituents at one or both of the remaining benzoic positions. Pyranocoumarin compounds, containing a six-membered ring, are analogous to the furanocoumarins. Pyrone-substituted coumarins include an unsaturated six membered ring containing one oxygen atom and a ketone group that are substituted in the pyrone (Lacy and O’Kennedy, 2004). The main chemical groups that are widely distributed in the genus Peucedanum are furanocoumarins, followed by angular-type pyranocoumarins (Takata, et al., 1990; Chang, et al., 2008; Ishii et al., 2008). Some of the isolated angular-type pyranocoumarins (seselins) from this genus are named praeruptorins, which comprise a free sugar khellactone skeleton (dihydroseselin) with different substituents at the two stereogenic centers (C-3’ and C-4’). According to their chemical structures, cis-khellactones are generally divided into 2 groups: the 3'R,4'R and 3'S,4'S configurations. The 3'S,4'S configuration is found mostly in P. praeruptorum and P. japonicum plants (Ren et al., 2013; Sarkhail et al., 2013b). The coumarin contents in several species are extremely similar, consisting largely of simple coumarins and linear and angular-type furanocoumarins. P. officinale, P. longifolium, P. ruthenicum, P. tauricum, P. morisonii and P. alsaticum are characterized by the presence of linear furanocoumarins, e.g., bergaptol, peucedanin and isoimperatorin. Peucedanum praeruptorum, P. japonicum, P. formosanum and P. harry-smithii var. subglabrum are most likely closely related because of the presence the angular-type dihydropyranocoumarins, e.g., praeruptorins A and B. A number of

Peucedanum species, e.g., decursivum, japonicum and praeruptorum, are unique in their high coumarin glycoside contents. Praeruptorins are considered the main components responsible for several pharmacological properties (Sarkhail et al., 2013b), such as calcium antagonist activity (Chang et al., 1994b), anti-platelet aggregation (Aida et al., 1995), Pglycoprotein inhibitory ability (Shen et al., 2012) and anti-HIV effects (Lee et al., 1994). (±)-Praeruptorin A (PA) (138) or dl-praeruptorin A (Pd-la) and (±)praeruptorin B (PB) (140) or dl-praeruptorin B (Pd-II, anomalin) are the most famous praeruptorins. They were found for the first time in P. praeruptorum. Because of a chiral preference in the herb, dextrorotatory isomers of praeruptorin A and praeruptorin B are naturally more abundant than their levorotatory enantiomers (Chen et al., 1979). To date, more than 50 coumarins have been isolated from P. praeruptorum (Chen et al., 1979; Song et al., 2011). The structure of coumarins from various species of Peucedanum (from 1 to 162) were displayed in Figures 2-9. 4.3. Other compounds Based on phytochemical studies, besides essential oils and coumarins, a range of flavonoids, phenols, phenylpropanoids, polyynes, glycosides, chromones, fatty acids, steroids, amino acids and nucleosides have been discovered in the Peucedanum species (Table 4). A few Peucedanum species contain fewer than 20 flavonoids, such as P. alsaticum (Skalicka-Wozniak et al., 2011), P. tauricum, P. officinale (Kuzmanov et al., 1981), P. ruthenicum (Kuzmanov et al., 1981; Alavi et al., 2009), and P. kenappi (Sarkhail et al., 2013a). The flavonoids in Peucedanum are mostly flavonols, including isorhamnetin, quercetin and kaempferol along with their glycosides.

Caffeic (171), chlorogenic (174), coumaric (176), ferulic (177) and vanillic acids (183) are the most prevalent phenolic acids in this genus (Manach et al., 2004; Macheix et al., 2005). Phenylpropanoid compounds have also been identified (Kong and Yao 2000; Yao et al., 2001; Hisamoto et al., 2004; Sajjadi et al. 2012). Two new phenylpropanoid glucosides, 3-(2-O-β-d-glucopyranosyl-4-hydroxyphenyl) propanoic acid (207) and methyl-3-(2-O-β-d-glucopyranosyl-4-hydroxyphenyl) propanoate (208), have been identified in the n-butanol soluble fraction of P. japonicum leaves (Hisamoto et al. 2004). To date, only a few investigations have analyzed the fatty acid profiles of Peucedanum species. For instance, the fatty acid compositions of seeds from five species of Peucedanum, including ruthenicum, chryseum, palimbioides, obtusifolium, and zedelmeierianum, were determined by Akpinar et al. (2012). Oleic acid (C 18:1 ω-9, 31.28% to 68.06%) (217), linoleic acid (C 18:2 ω-6, 15.99% to 33.74%) (214) and palmitic acid (C 16:0, 5.78% to 14.68%) (218) are the major fatty acids in the seed oils of these species. In P. palimbioides oil, oleic acid (23.57%) is a major compound. The polyyne compound falcarindiol (238) (see Figure 12), a potential anticancer component of some vegetables, such as carrots, parsley, celery, parsnip and fennel (Purup et al., 2009), has been found in P. praeruptorum (Miyazawa et al. 1996). The isolated components from different Peucedanum species are listed in Table 4. A number of isolated compounds, including chromones, phenolic acids, phenylpropanoids and miscellaneous compounds, are displayed in Figures 10-12.

5. Pharmacological and toxicological aspects

In the Peucedanum genus, 12 species of Peucedanum (accepted or unresolved), including P. alsaticum, P. cervaria, P. decursivum, P. formosanum, P. galbanum, P. grande, P. graveolens, P. japonicum, P. officinale, P. ostruthium, P. praeruptorum and P. pastinacifolium, are used in traditional medicine. The validity of traditional applications of some Peucedanum species appears to be confirmed by biological and pharmacological studies. Several extracts of Peucedanum spp. and isolated compounds have been evaluated for their anti-inflammatory, antipyretic, cardiopulmonary,

neuroprotection,

anti-cancer,

antioxidant,

antityrosinase,

antimicrobial, amoebicidal, antihelmintic, antiplatelet aggregation, anti-diabetic and phototoxic effects. P. praeruptorum and P. japonicum extracts and their major compounds, e.g., praeruptorins, have been well studied. (±)-PA and (±)-PB are effective in several cellular and animal models of inflammatory mediator release and tumor cell lines, and the molecular mechanisms that drive these effects have been discerned in some detail. Therefore, these compounds are attractive for the discovery and development of anticancer and immunosuppressant drugs. An overview of the modern pharmacological investigations performed on these species is described in detail below. 5.1. Anti-inflammatory and antipyretic activities Airway hyperreactivity that causes periodic bronchoconstriction and obstruction is one of the significant characteristics of allergic asthma (Crimi et al., 1998). Ethanol extract of P. ostruthium roots showed significant dose-dependent inhibition activity in carrageenan-induced edema test in rats; at the dose of 120 mg/kg orally, it reduced edema up to 57%. In another investigation, the main isolated

compound, 6-(3-carboxybut-2-enyl)-7-hydroxycoumarin (20), showed approximately 50% and 61.8% inhibition of edema at concentrations 30 and 300 µg/kg, respectively. Both the extract and isolated coumarin strongly decreased prostaglandin E2 (PGE2), PGI2, and PGD2 in stimulated rabbit ears. The IC50 value of the extract and isolated coumarin in 5-lipoxygenase assay, respectively, were 66 µg/mL and 0.25 µM. The extract and coumarin have been characterized as dual inhibitors of cyclooxygenase and 5-lipoxygenase activity. On the other hand, both of them showed antipyretic effects on yeast-induced fever in rat. However, 6-(3-carboxybut-2-enyl)-7hydroxycoumarin was more potent than acetylsalicylic acid (ASA) and indomethacin, as 400 µg/kg of this compound (i.p.) reduced the average of temperature by 2.1 °C after three hours, while ASA at dose of 160 mg/kg decreased the hyperthermia by 2.9 °C after two hours (Hiermann and Schant, 1998). The P. praeruptorum coumarin fraction (CPPD) significantly suppressed airway hyper reactivity in a dose-dependent manner in the presence of lung resistance induced by acetylcholine chloride in experimental mice. In addition, the effect of a high dosage of CPPD was comparable with that of dexamethasone, which was consistent with a previous report of the attenuation of acetylcholine-induced bronchoconstriction in rabbits by CPPD in vitro (Zhao et al., 1999). Zhang et al. (2005b) explained the significant anti-tussive and anti-inflammatory effects of the major components of P. praeruptorum. Yu and co-workers (2011) reported that the anti-inflammatory effect of (±)-PA-(138) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells may be due to inhibition of NF-κB signaling. (±)-PA inhibited nitric oxide (NO), TNF-α and IL-1b production in a dose-dependent manner. (±)-PA treatment at 25 mg/mL inhibited LPS-stimulated NO production up to 54%. Moreover, (±)-PA treatment at the same dose had a 42% and 54% inhibitory effect on

TNF-α and IL-1b production, respectively. (±)-PA also inhibited iNOS expression at the levels of protein and mRNA. Treatment with (±)-PA showed inhibitory effects on TNF-α and IL-1b mRNA expression in LPS-stimulated RAW264.7 cells. Therefore, (±)-PA can decrease the pro-inflammatory mediator release and display antiinflammatory effects. In another study, Xiong et al. (2012) reported the inhibitory effect of CPPD, containing praeruptorins, on allergic airway inflammation and T helper cell type 2 predominant responses in BALB/c mice (Xiong et al., 2012c). (±)PA has also shown potent anti-inflammatory effects in a murine model of chronic asthma.

(±)-PA

significantly

reduced

airway

inflammation

and

airway

hyperresponsiveness by reducing IL-4 IL-5, IL-13 and leukotriene C4 (LTC4) in bronchoalveolar lavage fluid (BALF) and immunoglobulin (Ig) E in serum. Moreover, this compound suppressed the expression of some factors involved in inflammatory responses, such as transforming growth factor β (TGF-β1). It inhibited eotaxin protein and mRNA expression, IκBα degradation, NF-κB nuclear translocation, NF-κB DNAbinding activity, and RelA/p65 phosphorylation, as well as up-regulating Smad7 in lung tissue and INF-γ in BALF (Xiong et al., 2012a,b). Praeruptorins (+)-PA (PC) (139), (+)-PB (PD) (141), and PE (142) showed anti-inflammatory activity in LPS-stimulated RAW264.7 murine macrophage cells by inhibiting STAT3/NF-κB signaling. All of those compounds significantly decreased lipopolysaccharide (LPS)-induced production of NO, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and mRNA and protein expressions of inducible NO synthase. Both PD and PE had higher anti-inflammatory activity than PC (Yu et al., 2012). Recently, two studies evaluated the effects of praeruptorins C (139), D (141), E (142) and (±)-PA (138) on LPS-induced pulmonary inflammation. Pretreatment with 80 mg/kg/orally of both PD and PE significantly decreased the total cell and

PMN counts and decreased TNF-α and IL-6 (pro-inflammatory cytokines) in bronchoalveolar lavage fluid, while the effective doses of (±)-PA and PC were 320 mg/kg. PD and PE at doses of 80 mg/kg decreased TNF-α up to 51% and 56%, respectively, and thereby suppressed the release of IL-6 up to 51% and 59%, respectively. In addition, PD and PE improved pathologic changes in the lung and inhibited the NF-κB activation in acute lung injury induced by LPS and HCl (Yu et al., 2012, Xiong et al., 2012b). 5.2. Antioxidant activity Free radicals play a major role in various chronic pathologies, such as cancer and cardiovascular diseases. Hisamoto and co-workers (2003) evaluated the antioxidant activity of the extracts and fractions obtained from P. japonicum leaves by two methods, DPPH radical scavenging followed by lipid peroxidation of the egg yolk phosphatidylcholine liposomes induced by 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH). As the n-butanol soluble fraction showed the highest activity, it was chromatographed for isolation of potent compounds. Isoquercitrin, rutin, neochlorogenic acid (172), cryptochlorogenic acid (173) and chlorogenic acid (174) were the main potent constituents of this fraction, which showed DPPH radicalscavenging activity (80.1% to 94.3%) after 5 h of reaction. Additionally, these compounds had a higher inhibitory activity in lipid peroxidation of the phosphatidylcholine liposome induced by AAPH than α-tocopherol and L-ascorbic acid (Hisamoto et al., 2003). Afterward, two compounds isolated from P. japonicum leaves,

2-(4-hydroxy-3-methoxyphenyl) propane-1,3-diol (206) and 3-O-β-d-

glucopyranosyl-2-(4-hydroxy-3-methoxyphenyl)

propanol

(209),

exhibited

an

appreciable DPPH radical-scavenging activity after 24 hours of reaction (73.9 to 87.9%), while α-tocopherol and L-ascorbic acid reacted with DPPH radical rapidly

(Hisamoto et al., 2004). These results confirmed that the analysis of the kinetics of compounds’ free radical scavenging is important for understanding their antiradical actions. Morioka et al. (2004) explained that the DPPH radical-scavenging effect of P. japonicum is one of the defense mechanisms against colon cancer cells. P. japonicum showed antioxidant activity in dose-dependent manner with an IC50 = 8777 µg/mL. The EtOAc fraction of P. knappii, which showed the highest radical-scavenging activity (SC50 = 36.4 µg/mL), was selected for the isolation and identification of major active

compounds.

Two

known

flavonol

glycosides,

rhamnetin-3-О-β-D-

glucopyranoside (197) and isorhamnetin-3-О-β-D-glucopyranoside (193), showed SC50 values of 0.29 µg/mL and 0.89 µg/mL, respectively, in a DPPH assay. The inhibitory effect of isorhamnetin-3-О-ß-D-glucopyranoside on DPPH radical was lower than that of quercetin (Sarkhail et al., 2013a). The methanol extract of P. graveolens (dill) showed a dose-dependent antioxidant effect in the DPPH assay. Three hundred microliters of it at 100 °C inhibited DPPH free radicals approximately 77%, and heating increased the antioxidant activity of dill extract significantly (P < 0.05) (Roy and Urooj, 2013). The antioxidant capacities of the essential oils of P. longifolium and P. palimbioides were assayed by four different methods: a ß-carotene/linoleic acid assay, a DPPH free radical scavenging, a method to measure their reducing power and a method to measure their chelating effect. P. palimbioides and P. longifolium oils showed strong antioxidant capacity (90.58% and 70.73%, respectively) in the βcarotene/linoleic acid assay at 2.0 mg/mL. At the same dose, P. palimbioides oil had a stronger chelating effect (90.39%) than P. longifolium (24.12%). At 1 mg/mL, the concentration-reducing power of P. palimbioides oil (0.248%) was greater than P. longifolium (0.104%), but neither of them exhibited activity as strong as the synthetic

antioxidants. Both oils showed moderate activity (41.87% to 47.26%) in DPPH free radical scavenging in comparison with the synthetic antioxidants (Tepe et al., 2011). 5.3. Antityrosinase activity Hisamoto et al. (2004) investigated the tyrosinase inhibitory activity of some isolated phenolic compounds from P. japonicum leaves. All compounds, including 2(4-hydroxy-3-methoxyphenyl) propane-1,3-diol (206) and 3-O-β-d-glucopyranosyl-2(4-hydroxy-3-methoxyphenyl) propanol (209) were weaker than kojic acid. Sarkhail and co-workers (2013a) showed that the most potent mushroom tyrosinase inhibition of the aerial parts of P. knappii extracts was achieved with the ethyl acetate fraction (IC50 =

517

µg/mL)

in

a

dose-dependent

manner.

Rhamnetin-3-О-β-D-

glucopyranoside (197) and isorhamnetin-3-О-β-D-glucopyranoside (193), the main flavonoids isolated from EtOAc, showed anti-tyrosinase activity with IC50 values of 27.95 µg/mL and 82.03 µg/mL, respectively. The inhibitory effect of rhamnetin-3-Оβ-D-glucopyranoside on tyrosinase was higher than that of kojic acid. 5.4. Anti-microbial, amoebicidal and antihelmintic activities The agar disc diffusion method was employed to determine the antimicrobial activities of P. paniculatum leaf and root oils against eleven bacterial strains (Vellutini et al., 2005). The results confirmed the antibacterial activity of oils on Staphylococcus aureus, Serratia marcescens, Micrococcus luteus, Bacillus subtilis, Enterobacter cloacae and Escherichia coli. However, the minimum inhibitory concentration (MIC) of leaf and root oils against S. aureus was 0.3% (3 mg/mL). Skalicka-Woźniak et al. (2007, 2009a) measured the antibacterial activity of essential oils from fruits of P. alsaticum and P. cervaria against 10 reference microorganisms by the agar dilution method using Mueller-Hinton agar. Among the Gram-positive bacteria, only B. subtilis and M. luteus were sensitive to these oils

(MIC = 2000 mg/L). Neither essential oil inhibited the growth of the Gram-negative bacteria E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, or Proteus mirabilis, even at the highest concentration tested (2000 mg/L). Moreover, they tested the essential oil and some of its components of P. alsaticum fruits against six Grampositive and Gram-negative bacteria. The Gram-positive strains S. epidermidis ATCC 12228, S. aureus ATCC 25923, S. aureus ATCC 6538, B. cereus ATCC 10876, B. subtilis ATCC 6633, Micrococcus luteus ATCC 10240 and the Gram-negative strains E. coli ATCC 25922, K. pneumoniae ATCC 13883, P. aeruginosa ATCC9027, and Proteus mirabilis ATCC 12453 were used. The MICs were determined by the agar dilution method. The essential oil had an effect against two Gram-positive bacteria, B. subtilis and M. luteus, with MIC = 2000 mg/L, while the oil and its components limonene, bornyl acetate, and α-phellandrene had no effect on the growth of any Gram-negative bacteria tested. On the other hand, 4-terpineol and linalool inhibited the growth of Gram-negative bacteria, with an MIC of 2000 mg/L, and showed similar activity against all the Gram-positive strains tested except S. epidermidis, against which 4-terpineol had no effect. At a concentration of 1000 mg/L, linalool, 4terpineol and bornyl acetate inhibited the growth of B. subtilis, B. cereus, and M. luteus but were inactive against the other strains tested. Limonene and α-phellandrene had no effect on the growth of any of the strains tested (Skalicka-Woźniak et al., 2008b). Fatty acid fractions isolated from the fruits of P. cervaria and P. alsaticum displayed moderate antibacterial activity that covered only Gram-positive bacteria, including staphylococci. The growth of Gram-negative bacteria and Candida species was not altered even at the highest extract concentrations applied (MIC > 4 mg/mL). P. alsaticum showed stronger antibacterial properties against Gram-positive bacteria,

with MIC values between 0.125 and 0.5 mg/mL, while P. cervaria extract inhibited the growth of Gram-positive strains, with MIC values between 0.25 and 2 mg/mL. At the same concentration (MIC = 0.25 mg/mL), both extracts were active only against M. luteus. Moreover, the minimal bactericidal concentration (MBC) for P. alsaticum and P. cervaria hexane extracts varied from 0.25 to 2 mg/mL and from 0.5 to 4 mg/mL, respectively. Oleic (217) and linoleic acids (214), the main compounds of both extracts, were responsible for the antibacterial activity against Gram-positive bacteria and indicated a synergistic antimicrobial effect (Skalicka-Woźniak et al., 2010). The methanol extract of P. graveolens (seed) exhibited moderate antimicrobial activity against Salmonella typhi (size of zone of inhibition ≥ 5-9 mm) by the disc diffusion method (Rani and Khullar 2004). The ethyl acetate fraction and praeruptorin A (138) from P. praeruptorum root had antimicrobial activity on Streptococcus agalactiae, with MIC values 250 and 100 µg/mL, respectively (Lu et al., 2001). Schinkovitz et al. (2003) screened P. ostruthium root for in vitro anti-mycobacterial activity against Mycobacterium fortuitum, a pathogen responsible for some infections in the lung and cutaneous soft tissue. The highest activity was found in the dichloromethane extract from P. ostruthium (MIC = 16 µg/mL). In the second step, two known compounds, named ostruthin (7) and imperatorin (39), were isolated from the active fraction. Ostruthin exhibited significant inhibitory activities against different strains of rapidly growing Mycobacteria, such as M. aurum, M. fortuitum, M. phlei and M. smegmatis, with MIC values between 3.4 to 6.7 µM, which were similar to those of ethambutol and isoniazid, but imperatorin showed no activity at concentrations up to 1.9 mM. The geranyl side chain of ostruthin increased lipophilicity in comparison with simple hydroxycoumarins such as umbelliferone

(15), which may to be an important factor for increasing activity. Umbelliferone showed weakly inhibitory activity (MIC = 0.79 mM). Twenty fractions from the ethyl acetate extract of P. ostruthium rhizome were applied to three pathogenic bacteria (B. cereus, E. coli, and S. aureus) to determine its antimicrobial activity using the disc diffusion method. The potent fraction had a large inhibition halo of 9.0 mm in diameter on B. cereus at a concentration of 16.2 µg/µL. E. coli and S. aureus showed no sensitivity to the ethyl acetate extract. Oxypeucedanin (46) and oxypeucedanin hydrate (47) were detected as the major compounds from this fraction, and while oxypeucedanin hydrate showed a significant antimicrobial activity against B. cereus at 220 µg, oxypeucedanin had not effect (Gökay et al., 2010). The acetone extract of the aerial parts and roots of P. nebrodense showed no antimicrobial activity in vitro at the concentration of 100 g/mL against the following Gram-positive and Gram-negative human-pathogenic bacteria: Staphylococcus aureus, Streptococcus agalactiae, B subtilis, E. coli, P. aeruginosa. It also had no effect against the antifungal bacteria Candida albicans and Candida tropicalis (Schillaci et al., 2003). The methanol extract and n-hexane fraction of P. zenkeri seeds showed antimicrobial activity. Imperatorin (39), bergapten (34) and isopimpinellin (42) were responsible for the antimicrobial action (Ngwendson et al., 2003). The methanol and MeOH/H2O (1: 1 v/v) extracts of P. salinum were screened for the antiviral and virucidal effects on human adenovirus type 5. The methanol extract of P. salinum at the concentrations of 0.5 and 1 mg/mL exhibited antiviral activity, with a decrease in virus titer of 2 log and 1.33 log, respectively. The MeOH/H2O extract (1:1 v/v) at concentrations of 1 and 2 mg/ml reduced the titer of the virus by 1.33 log and

1.5 log, respectively. On the other hand, the examined extracts showed no virucidal activity against adenovirus type 5 (Rajtar et al., 2012). The essential oil of P. ruthenicum fruits showed antimicrobial activity against various Gram-positive bacteria, such as S. aureus, S. epidermidis, and B. cereus, with MIC values of 0.03-0.29 mg/mL, using the agar dilution method. This oil showed no activity against the Gram-negative bacteria E. coli, P. aeruginosa, and Salmonella typhi (Alavi et al., 2005). The antibacterial activity of polar and nonpolar extracts from the roots of P. ruthenicum was studied using the cup plate technique to determine the growth inhibition of Staphylococcus aureus, S. epidermidis, P. aeruginosa and E. coli. The polar phase of the roots exhibited no significant antibacterial effect on the tested bacteria. On the other hand, the nonpolar phase showed inhibitory effect against S. aureus and E. coli, with MICs of 156.2 and 312.5 µg/mL, respectively, whereas it was inactive against S. epidermidis and P. aeruginosa, with MICs of > 1000 µg/mL (Sabri, et al., 2009). The antibacterial activity of the essential oil of whole parts of P. japonicum were studied against drug-susceptible and -resistant skin pathogens using the disc diffusion method (Yang et al. 2009). The MIC of P. japonicum against antibiotic-susceptible S. epidermidis CCARM 3709 was 0.13 µL/mL, while tetracycline-resistant S. epidermidis CCARM 3711 and M. furfur KCCM 12679 had minimum susceptibility to P. japonicum essential oil (MIC = 5 µL/mL). These results confirm that it is a good candidate for treatment of acne. All of the MeOH extracts of P. caucasicum, P. palimbioides, P. chryseum, and P. longibracteolatum at 32.0 mg/mL showed a time- and dose-dependent amoebicidal action on trophozoites and cysts, but the extract of P. longibracteolatum exhibited the most amoebicidal activity at 4.0 mg/mL or higher (Malatyali et al., 2012). The effects

of different extracts (petroleum ether, chloroform, ethyl acetate, methanol, water extract) of P. praeruptorum roots against Dactylogyrus intermedius were assayed by Wu et al. (2011), and the chloroform extract was the most effective after 48 hours of exposure, with EC50 = 240.4 mg/L. 5.5. Cardiopulmonary protection Vascular smooth muscle relaxation occurs through multiple mechanisms. Intracellular Ca2+ plays an important role in the endothelium-independent relaxation of vascular smooth muscle. Blockade of either extracellular Ca

2+

influx or internal

Ca2+ release efficiently relaxes vascular smooth muscle. On the other hand, endothelium-dependent relaxation is caused by various vasodilators present in endothelium and the secretion of NO, prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) (Xu et al., 2010). Based on traditional uses of P. ostruthium, Joa and co-workers (2011) evaluated the dichloromethane extract of P. ostruthium rhizomes for any antiproliferative activity in rat aortic vascular smooth muscle cells (VSMCs). This extract inhibited serum (10%)induced VSMC proliferation in a concentration-dependent manner. Additional identification and biological testing of its main components showed that the coumarin ostruthin (7) was the major antiproliferative substance; the IC50 for CH2Cl2 extract and ostruthin were, respectively 24 and 26 µg/mL. In an earlier study, the Ca2+antagonistic activity of P. ostruthium rhizome extract was confirmed in depolarized aortic strips by Rauwald et al. (1994). Aida and co-workers (1998) found that some isolated compounds from P. japonicum had non-competitive antagonistic effects on acetylcholine (Ach)- and histamine-induced contraction in the isolated guinea pig ileum. Moreover, these compounds showed noncompetitive

antagonist action on serotonin-induced

contraction of the rat uterus after injection of estradiol, while none of them inhibited the rabbit thoracic aorta contractions induced by epinephrine. These findings confirmed that P. japonicum has spasmolytic and antiallergic effects. Hao et al. (1996) reported that (±)-PA strongly relaxed ileum and tracheal smooth muscles. Afterward, Zaho and co-workers (1999) established the relaxant effect of the isolated pyranocoumarins from P. praeruptorum and P. decursivum roots on isolated rabbit tracheas and pulmonary arteries. PC (139), (±)-PA (138) and pteryxin (136) showed noticeable relaxant activities in tracheal preparations constricted with 40 mM KCl or 10 µM acetylcholine. The relaxant effects of PC, (±)-PA and pteryxin in KClconstricted tracheas are more effective than that in acetylcholine- or phenylephrineconstricted tracheas. These compounds at a dose of 30 µM completely relaxed tracheas constricted with 40 mM KCl, while P-II (peucedanocoumarin II) (131) at the same concentration created partial relaxation. These results confirmed that PC, (±)-PA and pteryxin are responsible for calcium antagonistic action and that the presence of acetoxy groups on C3’ and C4’ of dihydroseselin is critical for relaxing smooth muscles. Additionally, 8-methoxypsoralen (8-MOP) (54) showed a noticeable relaxant effect in the presence of 10 µM phenylephrine, without any effect in the presence of 40 mM KCl. This action may be partially cause by the inhibitory activity of 8-MOP on cytochrome P-450, known as the link between the store and plasma membrane Ca2+ pathways. Recently, Xu et al. (2010) demonstrated the bioactive compounds from P. praeruptorum roots, (±)-PA (138) are the main agents responsible for VSMC relaxation. Both (+)-PA (PC) (139) and (−)-PA showed a concentration-dependent relaxation activity in isolated rat aortic rings contracted by KCl. (+)-PA was more effective than (−)-PA because (+)-PA but not (−)-PA, in the molecular docking

studies, can bind to the pharmacophores of eNOS, thus stimulating NO/cGMP signaling. All these data strongly suggest that the relaxation of VSMCs by (+)-PA can be related to both endothelium-dependent and -independent mechanisms, while (−)PA only exerts an endothelium-independent effect. Additionally, (+)-PA improved the vascular hypertrophy by decreasing the area of smooth muscle cells (SMCs), collagen content and [Ca2+] in SMCs, and by increasing nitric oxide (NO) in reno-vascular hypertensive rats (Rao et al., 2002). Rao et al. (1998b) showed the effect of PC (139) and PE (142) in relaxing swine coronary arteries and decreasing contractility in guinea-pig left atria due to their calcium antagonist activity, but the calcium antagonistic activity of nifedipine was more potent than both PC and PE. In contrast, PC at doses of 2 mg/kg p.o. decreased the blood pressure in conscious normotensive and renal hypertensive rats and created significant drops in vertebral, left circumflex coronary and femoral vascular resistance in anesthetized dogs at doses of 20 and 100/µg/kg i.v. A preliminary clinical trial confirmed that PC was useful in the treatment of exertional angina pectoris. A dosage of 100 mg daily of PC decreased chest pain, the rate of angina attacks, the ST-segment changes, and the dose of nitroglycerine consumption. Chang and co-workers (1994b) reported that (±)-PA (138) was a cardiohemodynamic compound because of its Ca2+ channel blocker activity. The effect of (±)-PA on mean aortic pressure and rate-pressure product was about onetenth as strong as diltiazem. In a further study, (±)-PA showed calcium channel blockage and vasodilatory activity in cardio-hemodynamic modulation. Additionally, it regulated the expression of several immediate-early genes, including IL-6, Fas, Bax, and Bcl-2, and decreased neutrophil infiltration. These factors have significant effects on ischemic-reperfused myocardium, so (±)-PA has the effect of lowering the rate of

cardiomyocyte apoptosis (Chang et al., 2002). (±)-PA had a dose-dependent Ca2+ channel-blocking effect in single ventricular cells of guinea pig. Inhibitory rates of (±)-PA at doses of 1, 10, and 100 µM were 21%, 33.5%, 45%, respectively (Chang et al., 2007; Li et al., 1994). (±)-PA at 1.0 µmol/L during 30-min preventive perfusion reduced NF-κB activity from 0.98 ± 0.13 to 0.65 ± 0.17 (P < 0.05 vs. solvent) and decreased tumor necrosis factor-α (TNF-α) from 13.7 ± 6.1 µg/L to 9.4 ± 2.7 µg/L (P < 0.01 vs. solvent) in ischemic-reperfused (I/R) myocardium. This could be one of the molecular mechanisms of (±)-PA in cardioprotection (Wang et al., 2004). Injection of (±)-PA (0.1-3.0 mg/kg i.v.) on ischemic myocardial dysfunction in anesthetized dogs significantly and dose-dependently enhanced coronary blood flow and reduced mean aortic pressure, maximal rate of rise in left ventricular pressure, rate-pressure product and systemic vascular resistance, with a slight rise in heart rate. In addition infusion of 0.15 mg/kg/min (±)-PA for 30 minutes enhanced myocardial function in anesthetized open-chest dogs with regional myocardial dysfunction (Chang et al., 1994a). The CHCl3 fraction of P. japonicum root extract inhibited phenylephrine (PE)induced vasoconstriction at 100 µg/mL. The active isolated compound, (+)-PA (139), in the concentration range of 1–100 µM, dose-dependently relaxed PE pre-contracted aortic ring concentration, and this effect was partially endothelium dependent and mediated by the nitric oxide and cyclic GMP pathway. However, indomethacin, a cyclooxygenase inhibitor, had no effects on the action of (+)-PA. Atropine, a muscarinic receptor antagonist; triprolidine, an H1 histaminergic receptor antagonist; and propranolol, a β-adrenoceptor antagonist, had no significant effects on the actions of this compound, so its vasorelaxant effect apparently is not mediated by any of these receptors. In addition, (+)-PA (PC) suppressed the high K+ (80 mM)-induced and Ca2+-dependent contractions in a dose-dependent manner. Based on these results, (+)-

PC seems to be a voltage-operated Ca2+ channel blocker rather than a receptoroperated Ca2+ channel blocker, but it weakly relaxed PE (142) pre-contracted aortic rings in the presence of nifedipine, a blocker of voltage-operated calcium channels. On the other hand, tetraethylammonium (TEA, a non-specific K+ channel blocker) did not affect the vasodilatory activity of compound against PE-induced contraction. Endothelium dependence and Ca2+ channel blockade are two of the multiple mechanisms involved in the vasorelaxant effect of this compound (Lee et al., 2002). Tammela et al. (2004) found that P. palustre root extract and isolate coumarins have calcium channel blocking activity, and the inhibition Ca2+ uptake of columbianadin was approximately 10-fold greater than verapamil. 5.6. Neuroprotection Four isolated coumarin compounds, praeruptorin A (138), xanthotoxin (58), psoralen (52), and bergapten (34), from chloroform extract of the root of P. japonicum showed inhibitory activities on monoamine oxidase in mouse brain with IC50 values of 27.4 µM, 40.7 µM, 35.8 µM, and 13.8 µM, respectively (Huong et al., 1999). A bioautographic anti-acetylcholine esterase (ACE)-inhibited TLC assay performed with CH2Cl2 root extract of P. ostruthium confirmed the presence of several ACE compounds. Among these isolated compounds, the coumarins were more active than peucenin (164), a chromone derivative. Ostruthol (45), a potent ACE coumarin, showed a white inhibition spot on TLC at concentration 0.001 µg, indicating it was approximately 10-fold more active than ACE inhibitor galanthamine (Urbain et al., 2005). Zhang et al. (2001) investigated the effect of (±)-PA (138) on ATP-sensitive potassium channels (KATP channel) in human cortical neurons. KATP channels are widely present in the CNS, and activation of KATP channels is one of the endogenous

mechanisms of protection against ischemia or hypoxia. (±)-PA was a potassium channel opener (KCO) that increased the extracellular K+ and caused cellular membrane hyperpolarization (Zhang et al., 2001). Yang et al. (2013) showed that (+)PA (PC) (139) at dose of 10 µM had a protective effect (92.5 ± 7.5%, P < 0.05 vs. NMDA alone) against loss of cellular viability in excitatory neurotoxicity mediated by NMDA in primary cortical neurons. In addition, PC increases the ratio of Bcl2/Bax in NMDA-injured neurons and inhibited neuronal apoptosis by reversing intracellular Ca2+ overload. PC inhibited GluN2B-containing NMDA receptors by exposure to NMDA but did not change the expression of GluN2A-containing NMDA receptors. These results suggest the neuroprotective activity of PC is partly related to the downregulation of the expression of GluN2B-containing NMDA receptors and regulation of the Bcl-2 family (Yang et al., 2013). Administration of osthole (9) at doses of 50, 100 and 150 mg/kg intraperitoneally (i.p.) had no significant effect on the anticonvulsant activity of two classical antiepileptic drugs (AEDs: phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock seizure (MES) model. Thus, osthole shows a neutral pharmacodynamic interaction with two classical AEDs drug (Łuszczki et al., 2011). 5.7. Antidiabetic effect Diabetic rats treated with hydro-alcoholic extract of the aerial parts of P. pastinacifolium at 500 mg/kg body weight for 30 days had significantly reduced serum total cholesterol, triglyceride and LDL-C, whereas HDL-C significantly increased, as with treatment glibenclamide treatment (Movahedian et al., 2010). The antidiabetic effect of the 80% EtOH extract from P. japonicum led to the isolation of one coumarin and one cyclitol compound. Peucedanol 7-O-β-Dglucopyranoside (26) showed 39% inhibition of postprandial hyperglycemia at the

dose of 5.8 mg/kg, and myo-inositol significantly reduced postprandial hyperglycemia by 34% (Lee et al., 2004). Okabe et al. (2011) reported that P. japonicum (PJ) was a safe and useful natural agent to reduce obesity or body weight. They fed a 10% and 20% of PJ (leaves & stems) diet to obese mice. This diet inhibited the body weight gain and fat accumulation in the abdominal and subcutaneous deposits after 4 weeks. PJ reduced serum and liver triglycerides and serum leptin in a dose-dependent manner without any harmful effects on the liver. Additionally, PJ increased fecal excretion of triglycerides, reduced the amount of saturated fatty acids, and improved the level of polyunsaturated and n-3 fatty acids in the liver. In another study, mice fed 10% dried powder of leaves and stems from PJ for 4 weeks had significantly decreased serum triglycerides (TG), leptin, abdominal fat, and adipocyte size. In addition, PJ significantly increased fecal excretion of TG, reduced the fecal excretion of bile acid, and tended to increase the fecal excretion of total cholesterol. On the other hand, enhancement of adipocyte differentiation and normalization of adipose tissue functionality were caused by upregulation of the PPARγ, FXRα, DGAT1, and ATGL genes in the PJT-fed mice (Nukitrangsan et al., 2011). Nukitrangsan et al. (2012) explained the anti-obesity effect of PJ leaves and stem in high-fat diet-induced obese mice. Animals were fed PJ powder or extracts of PJ in water, 50% ethanol or 100% ethanol. The 100% ethanol extract of PJ decreased serum and liver triglycerides and reduced fat accumulation, adipocyte size and lipase activity in vitro. Preliminary phytochemical analysis confirmed the presence of some anti-obesity phenolic compounds, including neochlorogenic acid (172), chlorogenic acid (174) and rutin (196), in PJ extract. These compounds may be responsible for decreasing the absorption of fat and modulating obesity-related gene expression in the liver, adipose tissue, and muscle.

5.8. Antiplatelet aggregation Jong et al. (1992) observed the significant antiplatelet aggregation activity of cis-3',4'-diisovalerylkhellactone (126) (at 50 µg/mL) from PJ. Additionally, some compounds isolated from the root of P. japonicum, including eugenin (163), (−)selinidin (152), (+)-pteryxin (136), imperatorin (39), bergapten (34), cnidilin (38) and (+)-visamminol (168), showed strong antiplatelet aggregation activity in vitro (Chen et al., 1996). 3',4'-Diisovalerylkhellactone diester (PJ-1) from the medicinal herb P. japonicum inhibited the aggregation and ATP release of rabbit platelets induced by PAF (platelet-activating factor) (2 ng/ml) and collagen (10 µg/ml), with IC50 values of approximately 56.3 µM and 89.4 µM, respectively. PJ-1 also inhibited the thromboxane B2 formation and the phosphoinositide breakdown caused by collagen and PAF, respectively. Briefly, the main antiplatelet effect of PJ-1 may be owed to its dual activities of blocking PAF receptor-induced activation and inhibiting phospholipase A2 (Hsiao et al., 1998). Polyacetylene (panaxynol) (223), seselin-type dihydropyranocoumarins ((–)cis-khellactone (119), (+)-anomalin (141)) and psoralen-type furanocoumarins (psoralen (52), xanthotoxin (58)) from the root extract of P. formosanum showed strong anti-platelet aggregation activities. (–)-Isosamidin (150), (+)-peuformosin (133), (+)-cis-3’acetoxy-4’-(2-methylbutyroyloxy)-3’,4’-dihydroseselin (158), and phydroxy-phenethyl ferulate (203) at 100 µg/mL completely or nearly completely inhibited platelet aggregation

induced

senecioylkhellactone

(+)-cis-3’-acetoxy-4’-(2-methylbutyroyloxy)-3’,4’-

(128),

by collagen.

(–)-cis-3’-Isovaleryl-4’-

dihydroseselin and p-hydroxyphenethyl ferulate (203) at 100 µg/mL reduced plateletactivating factor (PAF)-induced platelet aggregation. Of these isolated compounds, phydroxyphenethyl ferulate showed the strongest anti-platelet aggregation effect. This

benzenoid compound at 5 µg/mL completely inhibited the platelet aggregation activity, with IC50 values of 5.1, 10.5 and 99.4 µM for platelet aggregation induced by arachidonic acid (AA), collagen and PAF, respectively (Chen et al., 2008). The pyranocoumarins (±)-PA and (±)-PB antagonize platelet aggregation, particularly that induced by platelet-activating factor (PAF) (Aida et al., 1995). Praeruptorin C at dose of 20 mg/kg/day for 9 weeks increased the vascular hypertrophy by decreasing SMC size, collagen content, and SMC Ca2+ influx and increasing NO production in the thoracic aorta of renovascular and spontaneously hypertensive rats (Rao et al., 2001). 5.9. Anti-cancer activity Nishino et al. (1990) considered the effect of (±)-PB on the in vivo tumorpromoting

action

of

12-O-tetradecanoylphorbol-13-acetate

(TPA)

in

7,12-

dimethylbenz[a]anthracene-initiated mouse skin. Administration of 10 µmol/painting of (±)-PB before the TPA treatment inhibited tumor formation for up to 20 weeks of tumor promotion. The CHCl3 extract of the PJ roots showed cytotoxic activity against the P-388 lymphocytic leukemia system, with an ED50 of 7.6 pg/ml. Furthermore, (+)PA has cytotoxicity activity on P-388 lymphocytic leukemia system in culture, with an ED50 of 2.6 pg/mL (Chang-Yih et al., 1991, 1992). Cytotoxic pyranocoumarins, including (+)-trans-khellactone (120), (+)-trans-4’-acetyl-3’-tigloylkhellactone (122) and (+)-PA, isolated from the chloroform extract of the aerial parts of PJ showed inhibitory activity against P-388 lymphocytic leukemia cells, with EDSDs of 2.8, 1.7 and 2.6 pg/mL, respectively (Chang-Yih et al., 1991). In another investigation, the CHCl3 extract of the PJ roots exhibited cytotoxic activity against the P-388 lymphocytic leukemia system, with an ED50 of 7.6 pg/mL. Moreover, two isolated pyranocoumarins, (−)-cis-khellactone and (+)-PA, had a cytotoxic effect on the P-388

lymphocytic leukemia in cell cultures, with an ED50 of 2.8 and 2.6 pg/mL, respectively (Chang-Yih et al., 1992). Morioka et al. (2004) investigated the chemopreventive effects of PJ by counting both aberrant crypt foci (ACF) and β-catenin-accumulated crypts (BCACs) as biomarkers of rat colon carcinogenesis. They studied the effect of PJ on the cell proliferation stimulated by azoxymethane (AOM). The number of ACF in the groups with 0.2 and 1% PJ (approximately 3 ACF) was significantly lower than control (10.8 ± 4.9, P < 0.05), and the mean number of BCACs in both treated groups (median 0.8/cm2/rat) was lower than that in the control group (2.138 ± 0.54/cm2/rat; P < 0.0001). Moreover, proliferating cell nuclear antigen (PCNA) labeling considerably decreased in both treated groups in comparison to control. These results confirmed the chemopreventive activity of PJ on the initial stage of colon carcinogenesis through inhibition of both ACF formation and accumulation of β-catenin by decreasing the cell proliferation and antioxidant activity. Kong et al. (2003b) studied the cytotoxic activity of (±)-PA both on RAW264.7 cells and starch-elicited primary mouse peritoneal macrophages. RAW264.7 and primary mouse macrophages treated with (±)-PA in doses ranging from 1 to 100 mg/mL had no effect on cell viability. In addition, (±)-PA had no cytotoxic activity in doses ranging from 1 to 60 mg/mL. These findings confirmed the good safety profile of (±)PA in vitro (Kong et al., 2003b). Zhang et al. (2003) found that (+)-PA and (-)-PA significantly induced HL-60 (human promyelocytic leukemia) cell differentiation toward both the myelocytic and monocytic lineages, making both enantiomers potential components of leukemia treatments. The effect of (±)-PA on induction of differentiation in HL-60 cells was time- and dose-dependent. Stimulation with 20 µg/mL (±)-PA for 72 hours decreased

cell growth by 90%, and cell cycle analysis showed a higher proportion of G1-phase cells compared to control. In another study, (+)-PA triggered mitochondria-mediated apoptosis in HL-60 cells and exhibited a dose-dependent apoptotic effect at 10-30 pg/mL on DNA fragmentation, with involvement of the extracellular signal-regulated kinase (ERK), c-Jun n-terminal kinase (JNK) and p38 MAPK pathways. (+)-PA elevated Bax protein level and mitochondrial-bound Bax and increased the Bax:Bcl-2 ratio, causing the loss of mitochondrial membrane potential and cytochrome c release (Fong et al., 2004). Wu et al. (2003) reported that pyranocoumarins, PA, in two conformational forms induced cell death through apoptotic mechanisms, with an IC50 of 41.9 ± 2.8 and 17.3 ± 8.2 µM for drug-sensitive KB-3-1 and multidrug resistant (MDR) KB-V1, respectively. Administration of pyranocoumarins with anti-tumor drugs, such as doxorubicin, paclitaxel, puromycin or vincristine, to the MDR KB-V1 cell line exhibited a synergistic effect, but not in drug-sensitive KB-3-1 cells. After 6 hours of pyranocoumarin treatment, doxorubicin accumulation improved in KB-V1 cells by 25%. However, in KB-V1 cells treated with different doses of pyranocoumarins for 24 hours had suppressed expression of P-glycoprotein at both the protein and mRNA levels. Moreover, pyranocoumarins rapidly reduced the cellular ATP content in a dose-dependent manner in KB-V1 cells. Lately, the synthesis of new derivatives of (3'S,4'S)-cis-khellactone coumarins have received much attention in the search for more potent compounds against tumor cells and HIV (Ren et al., 2013). Shen et al. (2006) have reported that a new semisynthetic compound, (±)-3’-O,4’-O-dicinnamoyl-cis-khellactone (DCK), is more effective than (±)-PA or verapamil in reversing Pgp-MDR. Interestingly unlike (±)PA, which suppresses Pgp expression, DCK does not but instead binds directly to

Pgp. The structure-activity relationship of two new semi-synthetic methoxylated compounds, (±)-3’-O,4’-O-bis(3,4-dimethoxycinnamoyl)-cis-khellactone (DMDCK) and (±)-3-O-bis(4-methoxycinnamoyl)-cis-khellactone (MMDCK), was studied by Fong et al. (2008). Unlike PA, which downregulated Pgp expression, neither DMDCK nor DCK suppressed Pgp expression but instead bound directly to Pgp. Methoxy substitution of the aromatic rings significantly enhanced the interaction between Pgp and pyranocoumarins and affected the Pgp-MDR reversing action, while 4-methoxy substitution only slightly decreased the activity. DMDCK was a good Pgp modulator because of its higher Pgp-MDR reversing activity and lower cytotoxicity (Fong et al., 2008). The 3',4'-cis-configuration of aromatic acyls was more effective than their trans-isomers in the MDR-reversing capability of pyranocoumarins (Shen et al., 2012). Furthermore, the rigid stereochemistry of 3'R- and 4'R-configured khellactone derivatives is necessary for their anti-HIV effect (Xie et al., 1999). The methanol extract of P. praeruptorum at 300 µg/mL decreased the growth of SGC7901 human gastric cancer cells by 51.2% (P < 0.01). This effect was due to the high concentrations of PA and PB in the extract. Both PA and PB had cytotoxic and antiproliferative activities on the SGC7901 cells. In addition, the combination of PA at 100 µM and doxorubicin (DOX) at 0.25 or 0.5 µM inhibited SGC7901 cell growth by 55.4% or 62.8% (P < 0.01 vs. DOX alone), respectively, and decreased the dose of DOX necessary for the desired effects in chemotherapy (Liang et al. 2010). In vitro, the acetone extract of the aerial parts and roots of P. nebrodense had antiproliferative effects against K562 (human chronic myelogenous leukemia) and L1210 (murine leukemia) cell lines, with IC50 values of 0.27 g/mL, compared to only a moderate activity on HL-60 (human leukemia) cells, with an IC50 value of 14.0 g/mL (Schillaci et al., 2003). Two aliphatic esters, 1,2-dipalmitoyl-3-glucosyl glycerol

(222) and 1,6-dihydroxy-hexane-bis-palmitoyl ester (221), were isolated from the roots of P. ledebourielloides and showed potential effects against the human gastric carcinoma SGC-7901, human colon cancer HT-29, and human promyelocytic leukemia HL-60 cancer cell lines. 1,2-Dipalmitoyl-3-glucosyl glycerol displayed more activity against HT-29 (IC50 = 0.21 µg/mL) than 1,6-dihydroxy-hexane-bispalmitoyl ester and 5-fluorouracil (standard), while 1,6-dihydroxy-hexane-bispalmitoyl ester was more potent in inhibiting HL-60 (IC50 = 0.49 µg/mL) in comparison to other tested compounds (Jiang et al., 2010). In a sulforhodamine B cytotoxicity assay, the IC50 values of (±)-PA on drugsensitive KB-3-1 (human oral epidermoid carcinoma) cells and KB-V1 (its multidrug resistant (MDR) subline) cells were 17.26 ± 8.24 µM and 41.91 ± 2.80 µM, respectively. However, the IC50 of doxorubicin was 3.05 ± 0.28 µM for KB-V1 and 0.06 ± 0.01 µM for KB-3-1. DNA fragmentation analysis established that pyranocoumarins induced cell death through apoptotic mechanisms (Wu et al., 2003). A number of natural and synthesized components have been screened for their Pglycoprotein (Pgp)-inhibiting property. Though Pgp has a significant role in protecting living tissues from damage by extruding xenotoxics out of cells, its overexpression can reduce the cellular levels of anticancer drugs and cause multidrug resistance (MDR) in tumor cells (Krishna and Mayer 2000). Furanocoumarin peucedanin from P. tauricum fruits at a dose of 15 µg/mL inhibited heat-shock protein (Hsp) 72 and Hsp 27 expression by 77.5% and 74.0%, respectively, in HeLa B human carcinoma cells. The incubation time and concentration of peucedanin affected the processes of apoptosis and necrosis and the morphology of HeLa cells (Bartnik et al., 2006).

5.10. Phototoxicity Many studies, both in vitro and in vivo, have been performed on the photoreactivity of coumarins. Some of these compounds can be applied for hyperproliferation skin diseases such as psoriasis. Furanocoumarins, including xanthotoxin (58), psoralen (52), bergapten (34), isopimpinellin (42) and imperatorin (39), have photosensitization, phototoxic, mutagenic and photocarcinogenic properties (Campbell et al., 1994). Ojala et al. (1999) detected the phototoxicity of lyophilized extract of P. palustre leaf and a number of coumarins in a bioassay of Artemia salina. Umbelliferone (15) and athamantin (80) had neither toxic nor phototoxic properties, while the LC50 values (µg/mL) bergapten, psoralen, peucedanin (48), xanthotoxin and isopimpinellin were 0.05, 0.09, 5, 14 and 103, respectively. In addition, the LC50 of plant extract after flowering was more than before flowering because of the increased coumarin content in the flowering stage. The phototoxic activity of bergapten, psoralen and xanthotoxin increased with irradiation time, while they were not toxic to A. salina without radiation. In contrast, peucedanin was toxic to A. salina irrespective of the irradiation time. 5.11. Toxicity No behavioral effects or acute toxicity have been detected after oral administration of fractions or praeruptorins A and B from P. praeruptorum root in mice. Moreover, after intraperitoneal administration of high doses (1 g/kg) of the EtOAc fraction and (±)-PA, only delayed mortality was observed. In the cytotoxic assay against Artemia salina, the EtOAc fraction and praeruptorins A and B showed 40.2, 121.2 and 34.5 µg/mL IC50 values, respectively (Lu et al., 2001). Nishino and co-workers (1990) pretreated mice with (±)-PB at the dose of 10 µmol/painting for 20 weeks, which had no toxicity. The median lethal dose (LD50) of the extraction of P.

praeruptorum was over 5 g/kg in an acute toxicity test in mice (Xiong et al., 2012a,b). The general pharmacological evaluation of praeruptorins showed that oral administration of (±)-PA or (±)-PB did not irritate behavioral effects in mice, and no acute toxicity or mortality occurred at the dose of 1 g/kg (Lu et al., 2001). The methanol extract of the fruits of P. grande and a naphthyl labdanoate diarabinoside isolated from that extract had nephroprotective activity against gentamicin-induced nephrotoxicity in Wistar rats (Aslam et al., 2012).

6. Conclusion

The present review summarized the traditional medicine uses (TMUs) and phytochemical and pharmacological aspects of the genus Peucedanum. To date, over 300 molecules, including terpenoids, coumarins, flavonoids, phenolic acids, phenylpropanoids, glycosides, amino acids and essential oils, have been identified from Peucedanum plants. Because the botanical classification of Peucedanum species by anatomical and morphological features is difficult and some species are confused with other species, chemical constituents of essential oils and coumarins have been valuable as chemotaxonomic markers. In this review, we mentioned 58 Peucedanum species, of which only 37 species are accepted in this genus (The Plant List, 2013). Non-polar fractions, essential oils and coumarins are mainly responsible for antimicrobial activities. For example, P. alsaticum and P. cervaria fruits, which are consumed as antimicrobial agents in European local medicine, have shown antibacterial activity against Gram-positive bacteria (Skalicka-Woźniak et al. 2010). However, other traditional uses of P. alsaticum and P. cervaria, e.g., diaphoretic, diuretic, stomachic and sedative actions, have not been investigated. The anti-

bacterial activity of the essential oil from P. japonicum against the drug-resistant skin pathogen S. epidermidis confirmed its potential use as an alternative remedy for the treatment of acne and other skin infections (Yang et al., 2009). The doses between 1000 and 3000 mg/L of various oils or isolated compounds from Peucedanum plants had potential activity against some bacteria (Vellutini et al., 2005; Skalicka-Woźniak et al. 2007, 2009a) even though a few had MIC < 1000 (Lu et al., 2001; Alavi et al., 2005; Gökay et al., 2010). For example, ostruthin, a coumarin isolated from P. ostruthium rhizome, showed significant inhibitory activities against different strains of Mycobacteria, with MIC values between 3.4 and 6.7 µM. Furthermore, oxypeucedanin hydrate from the ethyl acetate extract of P. ostruthium rhizome showed significant antimicrobial activity against Bacillus cereus (Gökay et al., 2010). Some Peucedanum species usually associated with the presence of phenolic compounds, including phenolic acids, flavonoids and phenylpropanoids, have shown antioxidant and anti-tyrosinase properties. Rhamnetin-3-О-β-D-glucopyranoside (197) and isorhamnetin-3-О-β-D-glucopyranoside (193), the main flavonoids isolated from P. knappii, showed DPPH radical-scavenging and anti-tyrosinase activity (Sarkhail et al., 2013a). In addition, isoquercitrin, rutin, neochlorogenic acid (172), cryptochlorogenic acid (173) and chlorogenic acid (174), the main potent constituents of the n-butanol fraction of P. japonicum leaves, exhibited a significant DPPH radical-scavenging activity (Hisamoto et al., 2003). Throughout the present review, we found that some traditional medicinal uses of Peucedanum species have been validated and supported by pharmacological investigations, and most studies have focused on the roots of Peucedanum plants, which are rich in bioactive coumarins. In vitro and in vivo pharmacological studies

have revealed that coumarins or nonpolar extract/fractions are responsible for a range of activities, including anti-inflammatory, antidiabetic, anti-platelet aggregation, and antiproliferative

activities,

cardiopulmonary

protection,

neuroprotection

and

phototoxicity. For example, the roots of P. praeruptorum and P. decursivum, which are traditionally used for some respiratory diseases and pulmonary hypertension, were validated to possess vasorelaxant and antiallergic activity by pharmacological tests (Zhao et al., 1999). Moreover, the P. praeruptorum coumarin fraction suppressed airway hyperreactivity and had anti-inflammatory and anti-microbial effects (Zhao et al., 1999; Lu et al., 2001). The root of P. japonicum, which is prescribed against coughs, colds and antifebrile in Japanese local medicine, showed antiallergic and vasorelaxant activity in vivo (Aida et al. 1998; Lee et al., 2002). The antiinflammatory and anti-pyretic effects of P. ostruthium root validated its use in traditional medicine for inflammatory diseases such as ulcers and cancer (Hiermann and Schant, 1998). The effectiveness of P. praeruptorum in TCM in decreasing chest pain, presumably in angina pectoris and ischemic heart (Rao et al. 1988b), is due to the presence of some active pyranocoumarins ((±)-PA and PE), which have a significant vasodilating effect (Hao et al., 1996; Chang et al., 2002). The cardioprotective effects of (±)-PA and PE were mediated by its calcium antagonist activity and suppression of TNF-α, IL-6, Fas, Bax, Bcl-2 and NF-κB (Kim and Um, 2011). In addition, the praeruptorins (±)-PA (138), D (141) and E (142) had potent anti-inflammatory effects in vitro and in vivo in pharmacological studies (Yu et al., 2012; Xiong et al., 2012a,b). Based on the results of in vitro pharmacological research on (±)-PA, it is effective in the concentration range of 1-100 µM. The beneficial action of the extracts and coumarins in some chronic inflammatory diseases, such as

cardiovascular disease, asthma and cancer, may be related to their suppression of cyclooxygenase (COX) or/and lipoxygenase (LOX) activity, mediated by decreasing the production of NO, LT, TNF-α and reactive oxygen species (ROS). Columbianadin (82) from P. palustre root extract had calcium channel blocking

activity

(Tammela

et

al.

2004),

and

6-(3-carboxybut-2-enyl)-7-

hydroxycoumarin (20) from P. ostruthium root had significant anti-edema and antipyretic effects (Hiermann and Schant, 1998). A number of coumarins from Peucedanum, such as eugenin (163), (−)-selinidin (152), (+)-pteryxin (136), imperatorin (39), bergapten (34), cnidilin (38), (+)-visamminol (168) (Chen et al., 1996), cis-3',4'-diisovalerylkhellactone (126) (Jong et al., 1992), (–)-isosamidin (150), (+)-peuformosin

(133),

(+)-cis-3’acetoxy-4’-(2-methylbutyroyloxy)-3’,4’-

dihydroseselin (158), and p-hydroxy-phenethyl ferulate (203) (Chen et al., 2008) showed anti-platelet aggregation activity. The cytotoxic effects of some coumarins, such as PA (138) and PB (140) (Chang et al., 1991; Chang et al., 1992; Zhang et al. 2003; Liang et al. 2010), have prompted a noticeable increase in the number of structure-activity relationship studies (SARs). Thus far, a few semi-synthetic pyranocoumarins for improving the efficacy of these compounds have been prepared (Fong et al. 2008; Shen et al., 2012). In addition, these findings suggest that some pyranocoumarins, e.g., PA, have the remarkable potential to be developed into new chemotherapeutic agents to treat cardiopulmonary diseases and cancers. Unfortunately, clinical studies are lacking. Just one clinical trial has been performed on (+)-PA (PC) (139), which demonstrated its efficacy in the treatment of exertional angina pectoris. Although the pharmacokinetic profiles of praeruptorins in human and rat liver microsomes have been summarized, future studies in humans should be performed to establish their safety and efficacy.

Toxicological studies of Peucedanum species and their isolated compounds are limited. Most reports showed no toxicity or mortality at the effective doses (Nishino et al., 1990; Lu et al., 2001; Xiong et al., 2012a,b). However, furanocoumarins, including xanthotoxin (58), psoralen (52), bergapten (34), isopimpinellin (42) and imperatorin (39), caused photosensitization and showed phototoxic, mutagenic and photocarcinogenic properties under irradiation conditions (Campbell et al., 1994; Ojala et al., 1999). As hepatotoxicity associated with coumarins related to the formation of a coumarin 3,4-epoxide intermediate has been reported (Lake et al., 2002), additional studies are required to quantify the acute and chronic toxicity in animals before clinical trials. As mentioned above, TMUs of Peucedanum species have been investigated by some pharmacological and biological studies, but further studies are required to identify the individual compounds responsible for these activities, their mechanisms of action and their toxicity. In conclusion, throughout our literature review, we observed that the research on Peucedanum has focused on a few species and their active components. Therefore, the phytochemical and pharmacological profiles of other species should be analyzed to find new bioactive substances.

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of Peucedanum praeruptorum in rats by liquid chromatography tandem mass spectrometry. Phytomedicine 18, 527-532. Zhang C, Xiao YQ, Taniguchi M, Baba K, 2006. Studies on chemical constituents from roots of Peucedanum praeruptorum II. China Journal of Chinese Materia Medica (Zhongguo Zhong Yao Za Zhi). 31, 1333-1335. [Article in Chinese] Zhao, N.C., Jin, W.B., Zhang, X.H., Guan, F.L., Sun, Y.B., Adachi, H., Okuyama, T., 1999. Relaxant effects of pyranocoumarin compounds isolated from a Chinese medical plant, Bai-Hua Qian-Hu, on isolated rabbit tracheas and pulmonary arteries. Biological & Pharmaceutical Bulletin 22, 984-987. Zhao, D., Islam, M.N., Ahn, B.R., Jung, H.A., Kim, B.W., Choi, J.S., 2012. In Vitro Antioxidant and Anti-inflammatory Activities of Angelica decursiva. Archives of Pharmacal Research 35, 179-192. Zheleva, A., Soine, T. O., Bubeva-Ivanova, L., 1972. Natural coumarins V: Isolation of xanthalin and a new pyranocoumarin, peuarenine, from Peucedanum arenarium W.K. Journal of Pharmaceutical Sciences. 61, 1643-1644. Zheleva, A.B., Mahandru, M.M., Bubeva-Ivanova, L., 1976. Four new coumarins from the roots of Peucedanum arenarium. Phytochemistry 15, 209-210. Zheng, X. , Du, J., Xu, Y., Liao, D., Pettit, G. R., 2010. Cytotoxic lipid esters from Peucedanum ledebourielloides Medicinal Chemistry Research 19, 337-343. Zimecki, M., Artym, J., Cisowski, W., Mazol, I., Włodarczyk, M., Gleńsk, M., 2009. Immunomodulatory and anti-inflammatory activity of selected osthole derivatives. Zeitschrift für Naturforschung C 64, 361-368.

Table 1 Scientific names, status (Accepted (Ac), Synonym (Syn) and Unresolved (Un)) and synonym(s) of reported Peucedanum species in this article (according to the Plant List 2013). Peucedanum species

Status Synonym (s)

P. alsaticum L.

Ac

Cervaria alsatica (L.) Gaudin Cnidium alsaticum (L.) Spreng. Johrenia pichleri Boiss. Ligusticum alsaticum (L.) Link Peucedanum lubimenkoanum Kotov Pteroselinum alsaticum (L.) Rchb. Selinum alsaticum (L.) Crantz Xanthoselinum alsaticum (L.) Schur

P. arenarium Waldst. & Kit.

Ac

Peucedanum borysthenicum Klokov

(P. arenarium var. arenarium

Peucedanum borysthenicum Klokov ex

a

Schischk.

)

P. austriacum (Jacq.)

Ac

W.D.J.Koch

Ferula austriaca (Jacq.) Spreng. Ferula elegans Spreng. Ferula montana Spreng. Ferula rablensis Wulfen Pteroselinum austriacum (Jacq.) Rchb. Selinum austriacum Jacq.

P. cachrydifolia Boiss.b

NRc

NR

P. carvifolia Vill.

Ac

Peucedanum euphimiae Kotov Peucedanum chabraei var. podolicum

Todor P. caucasicum K. Koch

Un

Some data suggest that it is synonymous with Selinum caucasicum M.Bieb.

P. cervaria (L.) Cusson ex

Ac

Lapeyr.

Athamanta cervaria (L.) L. Athamanta decussata Gilib. Athamanta latifolia Viv. Cervaria glauca Gaudin Cervaria laevis Gaudin Cervaria nigra Bernh. Cervaria rigida Moench Cervaria rivini Gaertn. Ligusticum cervaria (L.) Spreng. Oreoselinum minus Garsault Oreoselis cervaria (L.) Raf. Peucedanum cervaria (L.) Lap.(Syn) Peucedanum glaucum (Lam.) Dum.Cours. Selinum cervaria L. Selinum glaucum Lam.

P. cervariifolium C.A. Mey.

Ac

P. chryseum (Boiss. & Heldr.)

Un

Peucedanum sintenisii H. Wolff

D.F.Chamb. P. coriaceum Rchb.

Ac

P. decursivum (Miq.) Maxim.

Syn

Angelica decursiva (Miq.) Franch. & Sav.

P. delavayi Franch.

Ac

Sinodielsia delavayi (Franch.) Pimenov & Kljuykov

P. dissolutum (Diels) H. Wolff Ac P. formosanum Hayata

Ac

Peucedanum terebinthaceum subsp. formosanum (Hayata) Kitag.

P. gabrielae R.Frey

Un

P.galbanum (L.) Benth. &

Syn

Notobubon galbanum (L.) Magee.

Hook. f. P. galbanum (L.) Drude P. grande C.B.Clarke

Un

P. graveolens (L.) C.B.Clarke

Syn

Anethum graveolens L..

Ac

Peucedanum hirsutiusculum var.

[Illegitimate] or P. graveolens (L.) Hiern P. harry-smithii var. subglabrum (Shan & M.L.

subglabrum Shan & M.L. Sheh

Sheh) Shan & M.L. Sheh P. japonicum Thunb.

Ac

P. knappii Bornm.

Un

Some data suggest that it is synonymous with Zeravschania knappii (Bornm.) Pimenov & Kljuykov.

P. lancifolium Lange

Ac

P. ledebourielloides K.T. Fu

Ac

P. longibracteolatum Parolly

Un

& Nordt.

Calestania lancifolia Koso-Pol.

Some data suggest that it is synonymous with Dichoropetalum longibracteolatum (Parolly & Nordt) Pimenov & Kljuykov

P. longifolium Waldst. & Kit.

Ac

P. longshengense Shan &

Ac

M.L. Sheh P. luxurians Tamamsch.

Un

P. medium Dunn var. garcile

NR

NR

P. morisonii Besser

Ac

Peucedanum songoricum Schischk.

P. nebrodense

Un

Some data suggest that it is synonymous

Dunnd ex Shan at Sheh

with Holandrea nebrodensis (Guss.) Banfi, Galasso & Soldano P. neumayeri (Vis.) Rchb.f.

Syn

Peucedanum arenarium subsp. neumayeri (Vis.) Stoj. & Stef.

P. obtusifolium Sm.

Ac

Ferula obtusifolia (Sm.) Spreng. Malabaila obtusifolia (Sm.) Boiss. Pastinaca obtusifolia (Sm.) DC.

P. officinale L.

Ac

Selinum officinale (L.) Vest

P. oligophyllum (Griseb.)

Ac

Dichoropetalum oligophyllum (Griseb.)

Vandas

Pimenov & Kljuykov Seseli oligophyllum Griseb.

P. oreoselinum (L.) Moench

Ac

Angelica oreoselinum (L.) M.Hiroe Athamanta diffusa Gilib. Athamanta divaricata Gilib. Athamanta divaricifolia Stokes Athamanta oreoselinum L. Cervaria oreoselinum (L.) Gaudin Oreoselinum majus Garsault

Peucedanum bourgaei Lange Selinum oreoselinum (L.) Crantz P. ostruthium (L.)

Ac

W.D.J.Koch

Angelica officinalis Bernh. Angelica ostruthium (L.) Lag. Imperatoria ostruthium L. Ostruthium officinale Link Selinum ostruthium (L.) Wallr.

P. palimbioides Boiss.

Un

Some data suggest that it is synonymous with Dichoropetalum palimbioides (Boiss.) Pimenov & Kljuykov

P. palustre (L.) Moench

Ac

Athamanta flexuosa Juss. ex DC. Athamanta pisana Savi Calestania palustris (L.) Koso-Pol. Callisace schiefereckii Hoffm. Selinum palustre L. Thyselium palustre (L.) Raf. Thysselinum palustre (L.) Hoffm.

P. paniculatum Loisel.

Ac

P. pastinacifolium Boiss. &

Un

Some data suggest that it is synonymous

Hohen.

with Zeravschania pastinacifolia (Boiss. &

(P. pastinacifolium Boiss. &

Hohen.) Salimian & Akhani

Husskne) P. petiolare Boiss.

Un

P. praeruptorum Dunn

Ac

P. rubricaule Shan & M.L.

Ac

Sheh P. ruthenicum M.Bieb.

Ac

Callisace ruthenica (M.Bieb.) Fisch. ex Hoffm. Ferula besseriana Spreng. ex DC. Ferula ruthenica (M.Bieb.) Spreng.

P. salinum Pall. ex Spreng.

Un

Athamanta tenuifolia Willd. ex Spreng. Conioselinum humile Turcz. ex Ledeb.

P. schottii Besser ex DC.

Ac

Dichoropetalum schottii (Besser ex DC.) Pimenov & Kljuykov Holandrea schottii (Besser ex DC.) Reduron, Charpin & Pimenov Trachydium schottii (Besser ex DC.) M.Hiroe

P. scoparium Boiss.

Un

Some data suggest that it is synonymous with Johrenia scoparia Boiss

P. sowa (Roxb. ex Fleming)

Syn

Anethum graveolens L.

Kurz P. tauricum M.Bieb.

Ac

P. terebinthaceum var.

Syn

deltoideum (Makino ex K.

Peucedanum deltoideum Makino ex K. Yabe

Yabe) Makino P. terebinthaceum (Fisch. ex Trevir.) Ledeb.

Ac

Kitagawia terebinthacea (Fisch. ex Trevir.) Pimenov Peucedanum paishanense Nakai Peucedanum terebinthaceum var.

paishanense (Nakai) Y. Huei Huang Peucedanum terebinthaceum var. terebinthaceum Selinum terebinthaceum Fisch. ex Trevir. P. turgeniifolium H. Wolff

Ac

Peucedanum pulchrum H. Wolff

P. verticillare (L.)

Ac

Angelica verticillaris L.

W.J.D.Koch ex DC.

Imperatoria verticillaris (L.) DC. Ostericum verticillare (L.) Rchb. Peucedanum altissimum (Mill.) Thell. [Illegitimate] Selinum verticillare (L.) Vest Thapsia altissima Mill. Tommasinia altissima (Mill.) Reduron

P. vittijugum Boiss.

Ac

Bunium minutifolium Janka Dichoropetalum minutifolium (Janka) Pimenov & Kljuykov Dichoropetalum minutifolium (Janka) Pimenov & Kljuykov Peucedanum minutifolium (Janka) Velen. Peucedanum vittijugum subsp. minutifolium (Janka) Kuzmanov & N.Andreev

P. vourinense (Leute) Hartvig

Ac

Peucedanum longifolium subsp. vourinense Leute

P. wawrae (wawrii) (H. Wolff) Su ex M.L. Sheh in

Ac

Seseli wawrae H. Wolff

R.H. Shan & M.L. Sheh P. wulongense Shan & M.L.

Ac

Sheh P. zedelmeyeranum Manden.

Un

P. zenkeri Engl.

Ac

a

Both names have been reported by Zheleva et al. (1972 and 1976). Actually, the

accepted name is P. arenarium. b

P. cachrydifolia Boiss. was not included in The Plant List 2013.

c

Not reported.

d

This variety (P. medium Dunn var. garcile Dunn) was not included in Plant List

2013. e

This name have been reported by Movahedian et al. (2010) and Sajjadi et al. (2012).

Table 2 The known traditional medical uses and local names of Peucedanum species from different countries. Peucedanum

Regions

speciesa

Local

Uses recorded and

names

references

NRb

Formulation/Mo de of usage

P. alsaticum

Polish

Expectorant,

Fruit

(L.)

and

diaphoretic, diuretic,

Central-

stomachic, sedative, and

Europea

antimicrobial

n

(Skalicka-Woźniak

agent et

al., 2010). P. cervaria

Polish

NR

Expectorant,

Fruit

(L.) Lapeyr

and

diaphoretic, diuretic,

Central-

stomachic, sedative, and

Europea

antimicrobial

n

(Skalicka-Woźniak

agent et

al., 2010). P.

China

decursivum (Miq.) Maximo

Radix

Dispels

and

Peucedani

relieves

Korea

(Qianhu)

reduce

wind-heat, cough

and

sputum,

treatment of colds and headaches,

dyspneal

fullness and tightness in the

chest,

respiratory

Root

diseases and pulmonary hypertention (Kong et al., 2010). Zi-Hue

Treatment of respiratory

Qian-Hu

diseases and pulmonary

Root

hypertension (Zhao et al., 1999; Liu et al., 2005). In TCM: remedy for thick phlegm, asthma, and upper respiratory tract

infections

in

traditional (Chen et al., 2008). In Korean medicine as an antitussive, analgesic, antipyretic, and coughs remedy (Zhao et al., 2012). P. formosanum Hayata

Taiwan

Taiwan

Coughs, fever, headache

Qian-Hu

and excessive sputum caused by colds (Chen et al., 2008).

Root

P. galbanum

South

Mountain

(L.) Benth. &

Africa

celery

Hook . f.

Abortificient treatment catarrh,

and

of

Infution of plant

vesical

kidney

and

bladder

ailments,

prostate

problem,

swelling of glands and retention

of

urine

(Campbell et al., 1994). P. grande

India

C.B. Clark

and Iran

Duku (Dughou in

Diuretic,

Fruit

Emmenagogue,

Persian),

Aphrodisiac,

Baphalle,

Demulscent,

wild carrot, Deobstruent,Urolithotrip Hingupatri

tic, Anti-Inflammatory, Antidote, oncoctive/Maturative (Farid

et

al.,

2012;

Aslam et al., 2012). P. graveolens India

Indian

In

(L.) C.B

name

colic

Clark

flatulence, and

hiccup,

Essential oil and

abdominal the distilled water

Shepu or

pain in children and in

dill

adults (Roy and Urooj,

of the fruit

2012). P. japonicum

Japan

Sore throat (Morioka et

Thunb.

(in

al., 2004).

Leave and Root

Ryukyu Islands) and Taiwan Korea,

Japanese

Treatment

Japan,

common

colds, headaches and as

China,

name:

an

of

cough,

antifebrile

and

and

botan-bofu

anodyne (Ikeshiro et al.,

Taiwan.

or Shoku-

1992; Lee et al., 2004;

Bohfuu P. officinale

Bulgari

(L.)

a and

Samodivsk a treva

Root

Yang et al., 2009). Cardio-tonic (Leporatti

Root, fruit:

and, Ivancheva, 2003).

decoction

Italy Finocchio di porco (Italy)

Root: Infusion Astringent, emmenagogue (Leporatti

and

Ivancheva, 2003) P. ostruthium Europe , (L.) W.D.J.

UK and

Koch

Austria

Masterwort Treatment (Radix

inflammatory diseases,

imperatoria tuberculosis, e)

of

stimulant,

as

a a

stomachicum, a diuretic for chronic indigestion, as well as a therapeutic

Rhizome

for typhoid, intermittent fever,

paralytic

conditions,

and

delirium

in

tremens.

Externally, the drug was applied as a powder (Butenandt and Marten, 1932;

Gökay

et

al.,

2010). P.

China

praeruptoru

and

m Dunn

Japan

Peucedani Radix

Treatment of respiratory diseases,

pulmonary

(Baihua

hypertension (Zhao et

Qianhu)

al., 1999; Wu et al., 2003; He et al., 2007), alimentary

and

bronchial disorders and chest pain, presumably including

angina

pectoris (Rao et al., 1988).

Treatment

coughs sputum upper

with and

of thick

dyspnea, respiratory

infections nonproductive

and cough

Root

and as antitussive and mucolytic

agents

(Chang et al., 2001; He et al., 2007; Liang et al., 2012; Song et al., 2011). Korea

Crude drug

Used mainly cough and

(Jeon Ho)

dyspnea in respiratory infections

(Ji

et

Root

al.,

2010). P.

Central

pastinacifoliu and

AlafeTofangchi

Anti-hyperlipidemic

Aerial parts

vegetable (Movahedian

m Boiss. &

Western

et al., 2010; Sajjadi et

Hausskn

Iran

al., 2012).

a

The scientific name of plant was reported by the authors in their original works.

b

Not reported.

Table 3 Chemical composition (rel. %) of the essential oils isolated from different parts (Aerial parts (A.p), Branches (B), Fl (flowers), Fruits (Fr), Leaves (L), Rhizomes/Roots (R), Seeds (Se) and Steams (St)) of Peucedanum species. Peucedanu

Region

m species

Extracti on

Plant part(s) of use

Referenc

Monoterpenes

Sesquiterpenes

es

Air dried A.p:

Air dried A.p:

Kapetan

(-)-α-pinene

Trace

os et al.

method( s)a P.

Central

alsaticum

Balkan

SD

(6.4%), (+)-α-

(2008)

pinene (15.0%), (+)limonene (8.2%). Austria

Fr: α-pinene

St and L: E-

Chizzola

(11-40%),

nerolidol (5-22%), (2012)

sabinene (16-

spathulenol (up to

34%) and β-

18%), dodecanal

phellandrene

(up to 7.5%) and

(12-31%).

caryophyllene oxide (up to 7%).

Poland

Fr (HS-

Fr (HS-SPME): β- Skalicka

HS-

SPME): α-

caryophyllene

-

SPME

pinene (4.9-

(8.5%-5.5%),

Woźniak

HD and

27.0%),

germacrene D

et al.

sabinene (29.3

(8.7-6.9%).

(2008)

- 27.6%),

Fr (HD): β-

limonene + β-

caryophyllene

phellandrene

(5.5%),

(25.8-13.9%),

germacrene D

bornyl acetate

(7.9%).

(0.3-5.4% Fr (HD): αpinene (20.7%), sabinene (22.0%), limonene + βphellandrene (18.7%) and bornyl acetate (5.6%). P.

Central

austriacum

Balkan

NR

Air dried A.p:

Air dried A.p: (-)-

Kapetan

(-)-α-pinene

E-caryophyllene

os et al.

(16.5%), (+)-

oxide (5.5%).

(2008)

α–pinene (8.0%), camphene (8.7%)

(-)-limonene (7.6%), tricyclene (7.7%). P. cervaria

Central Balkan

NR

Air dried A.p:

-

Kapetan

(-)-α-pinene

os et al.

(12.6%), (-)-

(2008)

sabinene (5.5%), (+)-βpinene (10.2%) myrcene (9.1%), ρcymene (7.7%), (+)limonene (11.5%). Austria

Fr, St and L: β- -

Chizzola

pinene (7-

(2012)

58%), α-pinene (7-22%), sabinene (up to 22%), and βphellandrene with limonene (6-21%).

Poland

HD and

R, Fr: α-pinene

-

Skalicka

HS-

(SPME, Nb:

-

SPME

32.7%, Gc:

Wozniak

29.4), (HD, N:

et al.

31.3%);

(2009)

sabinene (SPME: N: 38.6%, G: 36.9; (HD, N: vs. 31.0%) and β-pinene, (SPME: N:19.4%, G:24.4%), (HD: N:21.7%). A.p: α-guaiene

Bazgir et

cervariifoli

(11.9%), γ-

al.

um

muurolene

(2005)

P.

Iran

HD

-

(7.4%), viridiflorene (10.9%), αselinene (16.3%) and β-selinene (27.4%).

P.

South

galbanum

Africa

P.

South

japonicum

Korea

HD

HD

Fresh A.p: ρ-

Fresh A.p:

Campbel

cymene

xanthoxin,

l et al.

(38.7%).

psoralen

(1994)

A.p: α-pinene

-

Yang et

(24.68%), β-

al.

pinene

(2009)

(66.07%). P.

Central

Air dried A.p:

-

Kapetan

longifolium

Balkan

(-)-α-pinene

os et al.

(36.3%),

(2008)

camphene (7.6%), (-)-limonene (6.7%). Turkey

HD

A.p.: δ-3-

8-cedren-13-ol

Tepe et

carene

(33.74%),

al.

(6.38%).

myristicin

(2011)

(8.03%), germacrene-D (7.73%). P. neumayeri

Greece

HD

A.p: γ-

germacrene-D

Evergeti

terpinene

(2.55)

s et al.

(32.25%), αpinene (21.27),

(2012)

β-phellandrene (12.76), limonene (4.71%), ρcymene (4.71). NR

L: β-pinene

-

Figuéréd

P.

Serba and

officinale

Montene

and myrcene

o et al.

gro

limonene, α-

(2009)

pinene and sabinene. St: β-pinene and myrcene , limonene, αpinene and sabinene. Fl: αphellandrene, β-pinene and myrcene, limonene, αpinene and sabinene R: limonene, α-pinene and sabinene

Iran

HD

L: fenchone

-

Jaimand

(27.7%), (E)-β-

et al.

ocimene

(2006)

(18.7%) and βpinene (8.1%). Se: fenchone (32%), (E)-βocimene (17.8%), and (Z)-β-ocimene (9.4%). Grrece

HD

A.p: bornyl

-

Evergeti

acetate

s et al.

(81.13%)

(2012)

2, 3, 4trimethyl benzaldehyde (4.68%)limonene (2.78%). -

Kapetan

Central

Air dried A.p:

Balkan

Tricyclene

os et al.

(6.1%), (-)-α-

(2008)

pinene (38.7%), (-)-

sabinene (11.5%), β phellanderene (7.2%), (+)-βpinene (8.0%), myrcene (5.3%). P.

Central

(+)-α -pinene

oreoselinu

Balkan

(15.2%), (-)-β

os et al.

–pinene

(2008)

m

Trace

Kapetan

(10.1%), (δ)-3carene (16.9%), Terpinolene (6.9%). Air dried Fr:

Air dried Fr:

Motskut

oreoselniu

limonene

Trace amounts.

e and

m

(44.1-82.4%),

Nivinske

γ-terpinene

ne

(12.2-17.5%),

(1999)

P.

Lithuania

SD

β-pinene (8.514.5%), αpinene (5.18.3%). P.

Poland

HD

R: sabinene

Herb: β-

Cisowski

ostruthium

(35.2%) of

caryophyllene

et al.

which (+)

(16.1%) and α-

(2001)

sabinene

humulene

accounts for

(15.8%).

(96.54%). 4-terpineol

A coumarin

(26.6%) of

(osthole) detected

which (+) 4-

in both essential

terpineol

oils (5.5% in herb

accounts for

and 5.1% in

(65.8%).

rhizome oil).

Herb: sabinene (4.7%). enantiomers: (+) sabinene (4.7%), (-) limonene (4.4%), (-) βpinene (0.4%). P.

Turkey

HD

A.p: α-pinene

-

Tepe et

palimbioid

(35.45%) and

al.

es

β-pinene

(2011)

(20.19%). P. palustre

Germany

Fl: limonene

L: Z,E.α-

Schmaus

87.53%, γ-

farnesene (15.0%)

et al.

terpinene

and germacrene-D (1989)

9.15%,

(12.69%)

St: α-pinene

R: trans-

50.3%, γ-

sesquilavandulol

terpinene

37.2%

16.42, myrcene 13.54%, limonene 5.51% L: mycene (9.0%), transocimene (17.8%), cisocimene (7.28%). R: limonene 24.8% L: ir-regular

two sesquiterpene

Vellutini

paniculatu

monoterpenes,

diols, 4,5-epi-

et al.

m

β-

cryptomeridiol

(2005)

isocyclolavand

and 4(15)-

ulyl acetate

eudesmen-1b,6a-

(6.1%), β-

diol

P.

HD

cyclolavanduly l acetate

(16.1%) and βcyclolavanduly l isobutyrate (17.8%), βisocyclolavand ulyl isobutyrate (5.3%). R: βisocyclolavand ulyl acetate (15.8%) and bcyclolavanduly l acetates (13.9%), lavandulyl acetate (9.8), βisocyclolavand ulyl isobutyrate (7.3%), βcyclolavanduly l isobutyrate (6.2%), βisocyclolavand ulol (5.7%).

P. petiolare Iran

HD

R: geranyl

R: β-bisabolene

Mirza et

acetate (5.7%),

(31.3%), (E)-

al.

citronellyl

sesquilavandulol

(2005)

acetate (5.2%)

(20.5%),

sabinene (5.2%) L: sabinene (42.5%), αpinene (42.6%) and limonene (2.6%). Seed: α-pinene (47.3%), sabinene (45.9%). Iran

HD

A.p: sabinene

Trace

Rustaiya

(57.8%) and

n et al.

δ-3-carene

(2001)

(36.2%) . P.

Iran

ruthenicum

(Central)

HD

L: thymol

L: β-bisabulene

Alavi et

(18.29%),

(13.29%)

al.

ethyl-dimetyl-

Fl: germacrene-B

(2006b)

thiophen

(10.06%)

(8.69%),

Fr: caryophyllene

β-pinene

oxide (13.65%),

(6.05).

8, 9-

Fl: β-myrcene

dehydroisolongifo

(10.68 %),

lene (11.33%) and

sabinene

caryophylla-

(8.65), β-

4(12), 8(13)-dien-

phellandrene

5-β-ol (5.19%)

(6.69%), ρ-cymene (6.21), αpinene (5.49%). Fr: 1,8-cineol (11.15%), cis carveol (6.88), camphor (5.86%) and 1carvone (5.61%). P.

Iran

ruthenicum

(North)

HD

L: thymol

Fl: β -bisabulene

Alavi et

(57.79%),

(6.10%),

al.

lanceol (5.41%),

(2006a)

Fl: β-myrcene

germacrene-D

(6.82%)

(45%) and germacrene-B (18.5%) and γ-

lemene (9.64%) P.

Iran

HD

scoparium

Air dried A.p:

Air dried A.p.:

Masoudi

The mian

Trace

et al.

components of

(2004)

α-Pinene (39.6%), βpinene (23.9%) and βphellandrene (9.5%). P. tauricum Poland

HD

-

Fr: RI: 1529 -

Bartnik

35.9%, RI: 1526 -

et al.

27.2%, RI: 1537 -

(2002)

7.1%) were not identified. β- γ-gurjunene (5.6%), Germany

HD

tricyclene,

Fr: α-ylangene, α-

Tesso et

myrcene,

copaen, β-

al.

limonene, (Z)-

bourbonene,

(2005)

β-ocimene,

guaia-6,9-diene,

2,4(8)-p-

selina-5,11-diene,

menthadiene,

valerena-4,7(11)-

linalool

diene, γamorphene, γ-

humulene, αbulnesene, βelemene, (E)-βcaryophyllene, αguaiene, αhumulene, and γgurjunene. guaiane type sesquiterpene hydrocarbons guaia-1(10),11diene (1) and guaia-9,11-diene (2) were identified. P.verticilla re

Italian

HD

Fresh L and B:

Dried Fr:.β-

Fraternal

Sabinene

caryophyllene

e et al.

(39.6%) (E)-

(24.2%), (Z)-β-

(2000)

anethole

farnesene (12.8%)

(29.5%),

β-bisabolene

epicamphor

(9.0%) and β-

(7.8%), α-

Elemene (7.5%)

pinene (6.3%)

Fresh Fr: β-

and α-

caryophyllene

phellandrene

(5.6%). Fresh Fr: sabinene (63.0%), αphellandrene (9.3%) and β-myrcene (8.1%). Dried Fr: αphellandrene (20.8%). P. zenkeri

Cameroo

L: limonene

Menut et

n

(23.2%),

al.

myrcene

(1995)

(8.9%) and myristicin (7.6%) R: dillapiole (19.1%), δ-3carene (14.7%) and myristicin (9.0%). a

Different extraction methods, including HD (Hydro-Distillation), SD (Steam

Distillation), HS-SPME (Headspace Solid-Phase Micro Extraction) and NR (not reported).

b

N: Natural; c G: Garden.

Table 4 Isolated compounds from different parts (Aerial parts (A.p), Flower (Fl), Foliage (Fo), Fruit (Fr), Herb (H), Leaf (L), Root (R), Seed (Se), Stem (St) and Whole plant (W.p)) of Peucedanum species. No. Compounds

Part(s)a Peucedanum

References

species Simple coumarins 1

Isofraxidin

R

praeruptorum

Ishii et al. (2008)

2

Isoscopoletin

R

praeruptorum

Kong et al. (1996b)

3

Kallisteine A

R

paniculatum

Vellutini et al. (2007)

4

Mexoticin

R

delavayi

Yan et al. (2008)

5

Officinalin (Peuruthenicin)

R

ruthenicum

Soine et al. (1973)

R, L,

ruthenicum

Fl, Fr R, L,

(1981) officinale

Fl, Fr R, L,

Kuzmanov et al. (1981)

longifolium

Fl, Fr R

Kuzmanov et al.

Kuzmanov et al., (1981)

morisonii

Shults et al. (2003)

Fr

tauricum

Tesso et al. (2005)

A.p

luxurians

Chinou et al. (2007)

6

Officinalin isobutyrate

R

morisonii

Shults et al. (2003)

Fr

tauricum

Tesso et al. (2005)

A.p

luxurians

Chinou et al. (2007)

7

Ostruthin

R

japonicum

Chen et al. (1996)

R

ostruthium

Urbain et al. (2005)

Fr

cervaria

SkalickaWoźniak et al. (2009)

8

Osthenol

L

palustre

Ojala et al. (1999)

9

Osthole

L

palustre

Ojala et al. (1999)

R, H

ostruthium

Cisowski et al. (2001)

R

ostruthium

Zimecki et al. (2009)

10

Peucenol

R

morisonii

Shults et al. (2003)

11

(+)-Peucedanol

R

japonicum

Ikeshiro et al., (1993)

L

japonicum

Hisamoto et al. (2003)

12

Scopoletin

R

praeruptorum

Ishii et al. (2008)

R

harry-smithii var.

Li et al. (2009)

subglabrum Fr

cervaria

SkalickaWoźniak et al. (2009)

13

Stenocarpin

R

morisonii

Shults et al. (2003)

A.p

luxurians

Chinou et al. (2007)

14

Stenocarpin isobutyrate

R

morisonii

Shults et al. (2003)

A.p

luxurians

Chinou et al. (2007)

15

Umbelliferone

R, Fr,

longifolium

L, Fl, St R, Fr,

(1981) oligophyllum

L, Fl R, Fr,

Kuzmanov et al. (1981)

vittijagum

L, Fl Fr, L,

Kuzmanov et al.

Kuzmanov et al. (1981)

carvifolia

Kuzmanov et al.

Fl R, Fr,

(1981) ruthenicum

L, Fl, St R, Fr,

(1981) officinale

L, Fl, St L

Kuzmanov et al.

Kuzmanov et al. (1981)

palustre

Ojala et al. (1999)

R

praeruptorum

Kong et al., (1996b), Ishii et al. (2008)

R

wulongense

Kong & Zhi (2003)

R

delavayi

Yan et al. (2008)

W.p

decursivum

Zhao et al. (2012)

16

Umbelliferone 6-carboxylic

R

morisonii

acid

Shults et al. (2003)

W.p

decursivum

Zhao et al., (2012)

17

Umbelliprenin

R

praeruptorum

Takata et al.(1990), Kong et al. (1993)

L

palustre

Ojala et al. (1999)

Se

zenkeri

Ngwendson et al.

(2003)

18

5-Hydroxy-6-isopranyl

R

formosanum

Chen et al. (2008)

Fr

grande

Aslam et al.

coumarin 19

8-Carboxy-7-hydroxy

(2012) R

praeruptorum

Ishii et al. (2008)

R

ostruthium

Hiermann et al.

coumarin 20

6-(3-Carboxybut-2-enyl)-7hydroxy coumarin

(1996) R

ostruthium

Hiermann and Schantl (1998)

R

paniculatum

Vellutini et al. (2007)

21

7-Methoxy coumarin

Se

zenkeri

Ngwendson et al. (2003

Simple coumarin glycosides 22

Apiosylskimmin

R

praeruptorum

Ishii et al. (2008), Zhang et al. (2009)

23

Esculin

L

japonicum

Hisamoto et al. (2003)

24

Hymexelsin

R

praeruptorum

Chang et al. (2008)

25

Peujaponiside

R

japonicum

Ikeshiro et al. (1994)

26

Peucedanol 7- O-beta-D-

R

japonicum

glucopyranoside

Hata, et al. (1968), Ikeshiro et al.(1994), Lee et al. (2004)

L

japonicum

Hisamoto et al. (2003)

27

Rubricauloside

R

rubricaule

Rao et al. (1991)

28

Scopolin

R

praeruptorum

Okuyama et al. (1989)

29

Skimmin

R

praeruptorum

Okuyama et al. (1989)

30

Praeroside VI

R

praeruptorum

Chang et al. (2008), Ishii et al. (2008)

31

Praerosides VII

R

praeruptorum

Chang et al. (2008)

Linear furanocoumarins (Psoralen type) 32

Alloimperatorin

R

morisonii

Shults et al. (2003)

33

Alsaticocoumarin A

Fr

alsaticum

SkalickaWoźniak et al. (2009)

34

Bergapten

R

oreoselinum

Lemmich et al. (1970)

A.p

galbanum

Campbell et al., (1994)

R

palustre

Ojala et al. (1999)

R

japonicum

Huong et al. (1999)

R

Fr

medium var.

Huang et al.

gracile

(2000)

tauricum

Głowniak et al. (2002), Tesso et al. (2005)

R

praeruptorum

Zhang et al. (2006)

A.p

luxurian

Chinou et al. (2007)

A.p

tauricum

Bartnik and Głowniak (2007)

A.p

ruthenicum

Alavi et al. (2008)

R

harry-smithii var.

Li et al. (2009)

subglabrum 35

Bergaptol

R, Fr

ruthenicum

Kuzmanov et al. (1981)

R, Fr, L, Fl

officinale

Kuzmanov et al. (1981)

R, Fr,

longifolium

L, Fl R

Kuzmanov et al. (1981)

morisonii

Shults et al. (2003)

36

5-Methoxybergaptol

R

morisonii

Shults et al. (2003)

37

Byakangelicin

R

Se

medium var.

Huang et al.

gracile

(2000)

zenkeri

Ngwendson et al. (2003)

38

Cnidilin

R

japonicum

Chen et al. (1996)

A.p

luxurians

Chinou et al. (2007)

R

morrissonii

Szewczyk and Bogucka - Kocka (2012)

39

Imperatorin

R

palustre

Vuorela et al. (1989)

A.p

galbanum

Campbell et al. (1994)

R

palustre

Ojala et al. (1999)

R

decursivum

Xu and Kong (2001)

Se

zenkeri

Ngwendson et al. (2003)

R

ostruthium

Urbain et al. (2005)

R

praeruptorum

Zhang et al. (2006)

Fr

alsaticum

SkalickaWoźniak et al. (2009)

40

Isobyakangelicin angelate

R

palustre

Vuorela et al. (1988)

R

palustre

Ojala et al. (1999)

41

Isoimperatorin

R, Fr,

longifolium

L, Fl R, Fr

Kuzmanov et al. (1981)

officinale

Kuzmanov et al. (1981)

R

palustre

Vuorela et al. (1989), Tammela et al. (2004)

A.p

galbanum

Campbell et al. (1994)

R

japonicum

Chen et al. (1996)

R

palustre

Ojala et al.

(1999) Fr

tauricum

Głowniak et al. ( 2002)

R

morisonii

Shults et al. (2003)

A.p

luxurians

Chinou et al. (2007)

Fr

tauricum

Bartnik and Głowniak (2007)

Fr

alsaticum

SkalickaWoźniak et al. (2009)

R

ostruthium

Vogl et al. (2011)

42

Isopimpinellin

A.p

galbanum

Campbell et al. (1994)

R

palustre

Ojala et al. (1999)

Se

zenkeri

Ngwendson et al. (2003)

43

Komalin

A.p

galbanum

Campbell et al. (1994)

44

Notoptol

Fr

alsaticum

SkalickaWoźniak et al. (2011)

45

Osthrutol

R

palustre

Vuorela et al. (1989)

R

palustre

Ojala et al. (1999)

R

ostruthium

Urbain et al. (2005), Vogl et al. (2011)

46

Oxypeucedanin

R, Fr,

officinale

(1981)

L, Fl, St Fr, L,

longifolium

Fl R, Fr

Kuzmanov et al.

Kuzmanov et al. (1981)

ruthenicum

Kuzmanov et al. (1981)

R

palustre

Vuorela et al. (1989)

R

palustre

Ojala et al. (1999)

A.p

tauricum

Bartnik and Głowniak (2007)

Fr

alsaticum

SkalickaWoźniak, K. (2009)

R

ostruthium

Gökay et al. (2010), Vogl et al. (2011)

47

Oxypeucedanin hydrate

Fr, L,

longifolium

Fl R, Fr,

(1981) officinale

L, Fl, St R, Fr

Kuzmanov et al.

Kuzmanov et al. (1981)

ruthenicum

Kuzmanov et al. (1981)

R

japonicum

Chen et al. (1996)

R

palustre

Ojala et al. (1999)

F

tauricum

Tesso et al. (2005)

R

ostruthium

Urbain et al. (2005), Gökay et al. (2010)

A.p

tauricum

Bartnik and Głowniak (2007)

A.p

luxurian

Chinou et al. (2007)

48

Peucedanin

R

ruthenicum

Soine et al. (1973)

R, Fr,

longifolium

L, Fl R, Fr, L, Fl

Kuzmanov et al. (1981)

officinale

Kuzmanov et al. (1981)

R, Fr,

ruthenicum

L, Fl R

Kuzmanov et al. (1981)

morisonii

Shults et al. (2003)

Fl

tauricum

Tesso et al. (2005)

A.p

tauricum

Bartnik and Głowniak (2007)

A.p

luxurians

Chinou et al. (2007)

R

A.p

terebinthaceum

Ganbaatar et al.

var deltoideum

(2008)

ruthenicum

Alavi et al. (2008)

Fr

alsaticum

SkalickaWoźniak et al. (2009)

49

8-Methoxypeucedanin

R

ruthenicum

Kuzmanov et al. (1981)

A.p

tauricum

Bartnik and Głowniak (2007)

R

harry-smithii var.

Li et al. (2009)

subglabrum Fr

cervaria

SkalickaWoźniak et al.

(2009) 50

3′-Acetate of oxypeucedanin

R

ostruthium

hydrate 51

Phellopterin

Hiermann et al. (1996)

R

Se

medium var.

Huang et al.

gracile

(2000)

zenkeri

Ngwendson et al. (2003)

L

palustre

Ojala et al. (1999)

52

Psoralen

A.p

galbanum

Campbell et al. (1994)

R

japonica

Chen et al. (1996)

R

japonicum

Huong et al. (1999)

R

palustre

Ojala et al. (1999)

R

formosanum

Chen et al. (2008)

A.p

ruthenicum

Alavi et al. (2008)

R

harry-smithii var.

Li et al. (2009)

subglabrum Fr

grande

Aslam et al. (2012)

53

5-Methoxypsoralen

R

praeruptorum

Chang et al.

(1994) 54

8-Methoxypsoralen

R

praeruptorum

Kong et al. (1993), Zhao et al. (1999)

55

12-Methoxypsoralen

A.p

ruthenicum

Alavi et al. (2008)

56

5-Hydroxy-8-methoxy

A.p

ruthenicum

psoralen

Alavi et al. (2008)

Se

zenkeri

Ngwendson et al. (2003)

57

5,8-Dimethoxypsoralen,

R

praeruptorum

Kong et al. (1996b)

58

Xanthotoxin

A.p

galbanum

Campbell et al. (1994)

R, A.p

praeruptorum

Yi and Lingyi (1995)

R

R

harry-smithii var.

Chen et al.

subglabrum

(1996)

japonicum

Chen et al. (1996)

R

japonicum

Huong et al. (1999)

R

palustre

Ojala et al. (1999)

A.p

luxurian

Chinou et al.

(2007) R

formosanum

Chen et al. ( 2008)

Fr

grande

Aslam et al. (2012)

59

Xanthotoxol

R

palustre

Ojala et al. (1999)

Linear dihydro furanocoumarins (Dihydroporalen type) 60

Deltoin

R

japonicum

Chen et al. (1996)

R

R

terebinthaceum

Ganbaatar et al.

var. deltoideum

(2008)

harry-smithii var.

Li et al. (2009)

subglabrum R

decursivum

Xu and Kong (2001)

61

Kallisteine B

R

delavayi

Yan et al. (2008)

R

paniculatum

Vellutini et al.

(spirodihydrofurano-

(2007)

coumarin) 62

Marmesin (Nodakenetin)

A.p

galbanum

Campbell et al. (1994)

R

praeruptorum

Kong et al. (1994)

R

japonicum

Chen et al. (1996)

R

decursivum

Liu et al. (2005)

R

delavayi

Yan et al. (2008)

R

harry-smithii var.

Li et al., (2009)

subglabrum W.p

decursivum

Zhao et al. (2012)

63

Oreoselon

R

morisonii

Shults et al. (2003)

Linear dihydro furanocoumarin glycoside 64

Ammijin ((-)-Marmesinin)

R

praeruptorum

Okuyama et al. (1989)

65

Decuroside I

R

delavayi

Yan et al. (2008)

R

decursivum

Sakakibara et al. (1984), Matano et al. (1986)

66

Decuroside II

R

decursivum

Sakakibara et al. (1984), Matano et al. (1986)

67

Decuroside III

R

decursivum

Sakakibara et al. (1984), Matano et al. (1986)

68

Decuroside V

R

decursivum

Asahara et al.

(1984), Matano et al. (1986 ) 69

Decuroside IV

R

decursivum

Asahara et al. (1984), Matano et al. (1986)

70

Decuroside VI

R

decursivum

Xu and Kong (2001)

71

Isorutarin

R

decursivum

Yao et al. (2001)

R

praeruptorum

Okuyama et al. (1989)

72

Nodakenin

W.p

decursivum

Matano et al. (1986) Zhao et al. (2012)

73

Praeroside I

R

praeruptorum

Okuyama et al. (1989)

74

Rutarin

R

praeruptorum

Okuyama et al. (1989)

Angular-type furanocoumarins (Angelicin type) 75

Angelicin

H (Fl, L, St)

oreoselinum

Coste et al. (2011)

76

Oroselol

R

oreoselinum

Lemmich et al. (1970)

77

Pimpinellin

R

palustre

Vuorela et al. (1989)

R

palustre

Ojala et al. (1999)

R

ostruthium

Vogl et al. (2011)

Angular-type furanocoumarin glycosides 78

Peucedanoside A

R

praeruptorum

Li et al. (1994), Wu et al. (2003), Chang et al. (2007)

79

Peucedanoside B

R

praeruptorum

Chang et al. (2007)

Angular-type dihydrofuranocoumarins 80

Athamantin

R

oreoselinum

Lemmich et al. (1970)

81

Archangelicin

R

oreoselinum

Lemmich et al. (1970)

82

Columbianadin

A.p

luxurians

Chinou et al. (2007)

R

palustre

Ojala et al. (1999), Vuorela et al. (1989), Eeva et al. (2004), Tammela et al. (2004).

R

decursivum

Xu and Kong (2001)

Fr

cervaria

SkalickaWoźniak et al. (2009)

83

Columbianadin oxide

R

palustre

Ojala et al. (1999), Eeva et al. (2004).

84

Dihydrooroselol

R

oreoselinum

Lemmich & Gylle (1988)

85

(8S, 9R)-9-acetoxy-O-

R

oreoselinum

isovaleryl-8,9-

Lemmich et al. (1970)

dihydrooroselol 86

(8S, 9R)-9-acetoxy-O-

R

oreoselinum

senecioyl-8,9-

Lemmich et al. (1970)

dihydrooroselol 87

(8R, 9S)-2’ -angelyoyoxy-9isovaleryloxydihydrooroselol

R

oreoselinum

Lemmich & Gylle (1988)

88

(8S)-9-hydroxy-8,9-

R

oreoselinum

dihydrooroselol 89

(8S, 9R)-9-hydroxy-O-

Lemmich et al. (1970)

R

oreoselinum

senecioyl-8,9-

Lemmich et al. (1970)

dihydrooroselol 90

(8S, 9R)-9-isovaleryloxy-

R

oreoselinum

8,9-dihydrooroselol 91

(8R)-2’(methyl

Lemmich et al. (1970)

R

oreoselinum

Lemmich & Gylle (1988)

butyroyloxy)-8,9dihydrooroselol 92

(8S)-O-Senecioyl-8,9-

R

oreoselinum

dihydrooroselol 93

Isopeulustrin

Lemmich et al. (1970)

R

palustre

Ojala et al. (1999), Eeva et al. (2004)

94

Peucenidin

R

oreoselinum

Lemmich et al. (1970)

95

Peulustrin

R

palustre

Ojala et al. (1999), Eeva et al. (2004)

96

Vaginidin

R

oreoselinum

Lemmich et al. (1970), Lemich and Gylle (1988)

Angular-type dihydrofuranocoumarin

glycosides 97

Apterin

R

praeruptorum

Chang et al. (2007)

R

palustre

Ojala et al. (1999), Eeva et al. (2004)

L

japonicum

Hisamoto et al. (2003)

Linear type dihydropyranocumarins (Dihdroxanthyletin type) 98

3', 4'-Dihydroxanthyletin

R

decursivum

Yao et al. (2001)

R

harry-smithii var.

Li et al. (2009)

subglabrum 99

Decursin

Fr

terebinthaceum

Ganbaatar et al.

var. deltoideum

(2008)

100 Decursidin

R

decursivum

Liu et al. (2005)

101 (−)-Smyrinoll; (+)-

R

wulongense

Kong and Zhi

Decursinol 102 (+)-trans-Decursidinol

(2003) R

decursivum

Xu and Kong (2001)

103 (−)-methyl-Decursidinol

R

arenarium

Zheleva et al. (1972)

104 3'(S)-Acetoxy-4'(R)angeloyloxy-3', 4'-

R

wawrii

Kong et al. (2003)

dihydroxanthyletin R

decursivum

Xu and Kong (2001)

105 Decursitin B (xanthalin)

R

arenarium

Zheleva et al. (1972)

R

decursivum

Xu and Kong (2000)

106 Decursitin

R

decursivum

Kong et al. (2000)

R

decursivum

Xu and Kong (2000), Liu et al. (2005)

107 Decursitin D

R

decursivum

Yao and Kong (1999), Xu and Kong (2000), Yao et al. (2001)

108 Decurstin F

R

decursivum

Yao and Kong (2001)

109 Pd-C-III

R

decursivum

Sakakibara et al. (1982)

110 Pd-C-IV

R

decursivum

Yao and Kong (2001), Liu et al. (2005)

111 Pd-C-V

R

decursivum

Liu et al. (2005)

112 Peuarenine

R

arenarium

Zheleva et al.

(1972) 113 Peuarin

114 Peuarenarine

R

R

arenarium var.

Zheleva et al.

arenarium

(1976)

arenarium

Zheleva et al. (1972)

115 Peuchlorin

116 Peuchlorinin butyroyl

R

arenarium var.

Zheleva et al.

arenarium

(1976)

arenarium var.

Zheleva et al.

arenarium

(1976)

arenarium var.

Zheleva et al.

arenarium

(1976)

R

dissolutum

Wu et al. (2004)

R

japonicum

Chang-Yih

R

isokhellactone 117 Peucloridin

R

Linear type dihydropyranocumarin glycoside 118 3′(R)-O-β-DGlucopyranosyl-3′,4′dihydroxanthyletin Angular type dihydropyranocumarin 119 (−)-cis-Khellactone

(1992)

120 (+)-trans-Khellactone

R

formosanum

Chen, et al. (2008)

A.p

japonicum

Chang-Yih et al. (1991)

R

wulongense

Kong & Zhi

(2003) 121 (±)-cis-3′-Acetyl-4′-

A.p

japonicum

tigloylkhellactone 122 (+)-trans-4′-Acetyl-3′-

(1996) A.p

japonicum

tigloylkhellactone 123 (−)-trans-3′-Acetyl-4′-

Chang-Yih et al. (1991)

R

japonicum

senecioylkhellactone 124 3'-Angeloyloxykhellactone

Chen et al.

Chen et al. (1996)

R

praeruptorum

Kong et al. (1993)

125 Coumurayin

R

delavayi

Yan et al. (2008)

126 3’(S),4’(S)-diisovaleryloxy-

W.p

japonicum

Yamada et al.

3’,4’-dihydroseselin

(1974) A.p

japonicum

Jong et al. (1992)

A.p

japonicum

Ikeshiro, et al. (1992)

R

praeruptorum

Zhang et al. (2005c)

127 3’(S),4’(S)-disenecioyloxy-

R

japonoicum

3’,4’-dihydroseselin

Kong and Zhi (2003)

R

wulongense

Shigematsu et al. (1982)

128 cis-3'-isovaleryl-4'-

A.p

japonicum

Jong et al. (1992)

R

longshengense

Huang et al.

senecioylkhellactone 129 Longshengensin A

(1997)

R

wawrii

Kong et al. (2003)

130 Peucedanocoumarin I

R

praeruptorum

Takata et al. (1990), Kong et al. (1993), Kong et al. (1996b), Hou et al. (2009)

131 Peucedanocoumarin II

R

praeruptorum

Takata et al. (1990), Kong et al. (1993), Zhao et al. (1999)

132 Peucedanocoumarin III

R

praeruptorum

Kong et al. (1993)

R

japonicum

Chen et al. (1996)

R

R

medium var.

Huang et al.

gracile

(2000)

ostruthium

Vogl et al. (2011)

133 (+/-) Peuformosin

R

harry-smithii var.

Li et al. (2009)

subglabrum R

praeruptorum

Ruan et al. (2011), Zhang et al. (2011), Xiong et al. (2012a &

2012b) 134 Peujaponisinol A

R

japonicum

Ikeshiro, et al. (1993)

135 Peujaponisinol B

R

japonicum

Ikeshiro et al. (1992 & 1993)

136 Pteryxin

R

praeruptorum

Kong et al. (1993), Takata et al. (1990), Zhao et al. (1999), Wang et al. (2012)

R

japonicum

Chen et al. (1996)

R

terebinthaceum

Ganbaatar et al.

var. deltoideum

(2008)

137 Isopteryxin

R

dissolutum

Wu et al. (2004)

138 (±)-Praeruptorin A (Pd-Ia;

R

praeruptorum

Chang et al.

Longshengensin A)

(1994), Fong et al. (2008) R

Japonicum

Chen et al. (1996)

R

japonicum

Huong et al. (1999)

R

praeruptorum

Zhao et al. (1999), Lu et al.

(2001), Wu et al. (2003), Zhang et al. (2005a), Wu et al. (2009), Xu et al. (2010) R

harry-smithii var.

Li et al. (2009)

subglabrum 139 Praeruptorin C; (+)

A.p

japonicum

praeruptorin A

Chang-Yih et al. (1991)

R

praeruptorum

Rao et al. (1988), Zhao et al. (1999), Rao et al. (2001), Wu et al. (2003), Zhang et al. (2003), Xu et al. (2010), Yu et al. (2012)

140 (±)-Praeruptorin B

R

japonicum

(Anomalin; Pd-II)

Ikeshiro, et al. (1992)

R

praeruptorum

Aida et al. (1995), Zhang et al. (2005c), Hou et al. (2009), Wu et al. (2009), Xu et al. (2010),

Liang et al. (2012) R

wulongense

Kong and Zhi (2003)

R

formosanum

Chen et al. (2008)

R

delavayi

Yan et al. (2008)

R

harry-smithii var.

Li et al. (2009)

subglabrum 141 Praeruptorin D ((+)

R

praeruptorum

Yu et al. (2012)

R

praeruptorum

Rao et al. (1988),

Praeruptorin B) 142 Praeruptorin E ( wulongensin A)

Zhang et al. (2006), Hou et al. (2009), Yu et al. (2012) Se

zenkeri

Ngwendson et al. (2003)

143 Peujaponisin

R

japonicum

Ikeshiro et al. (1992)

144 Qianhucoumarin A

R

praeruptorum

Kong et al. (1993)

145 Qianhucoumarin B

R

praeruptorum

Kong et al. (1993)

146 Qianhucoumarin C

R

praeruptorum

Kong et al. (1993)

147 Qianhucoumarin D

R

praeruptorum

Kong et al. (1993), Kong et al. (1994), Liu et al. (2004)

148 Qianhucoumarin E

R

praeruptorum

Kong et al. (1994), Wu et al. (2009)

149 Qianhucoumarin I

R

praeruptorum

Kong et al. (1996a)

150 Isosamidin

R

formosanum

Chen et al. (2008)

151 Samidin

R

japonoicum

Ikeshiro, et al. (1994)

152 Selinidin

R

japonicum

Chen et al. (1996)

153 (±)-4'-Tigloylkhellactone

R

japonicum

Chen et al. (1996)

154 Turgeniifolin A (Pd-Ib)

W.p

turgeniifolium

Ding (1981)

R

praeruptorum

Hou et al. (2009), Kong et al. (1994), Yu et al. (2011), Zhang et al. (2011)

155 Turgeniifolin B

W.p

turgeniifolium

Ding (1981)

156 TurgeniifolinC

W.p

turgeniifolium

Ding (1981)

157 (−)-Visnadin

R

japonicum

Ikeshiro et al.

(1992) 158 (+)-cis-3’acetoxy-4’-(2-

R

formosanum

Chen et al. (2008)

R

praeruptorum

Takata et al.

methylbutyroyloxy)-3’,4’dihydroseselin Angular dihydropyrano coumarine glycoside 159 Praeroside II

(1988) L

japonicum

Hisamoto et al. (2003)

160 Praeroside III

R

praeruptorum

Takata et al. (1988)

L

japonicum

Hisamoto et al. (2003)

161 Praeroside IV

R

praeruptorum

Takata et al. (1988)

L

japonicum

Hisamoto et al. (2003)

162 Praeroside V

R

praeruptorum

Takata et al. (1988)

L

japonicum

Hisamoto et al. (2003)

Chromones 163 Eugenin

R

japonicum

Chen et al. (1996)

164 Peucenin

R

ostruthium

Urbain et al. (2005)

Linear Dihydro pyrano chromones 165 Divaricatol

Fr

alsaticum

SkalickaWoźniak et al. (2012)

166 Ledeburiellol

Fr

alsaticum

SkalickaWoźniak et al. (2012)

167 (−)-Hamaudol

R

japonicum

Chen et al. (1996)

R

168 (+)-Visamminol

R

medium var.

Huang et al.

gracile

(2000)

japonicum

Chen et al. (1996)

Dihydro furano chromones 169 Prim-O-glucosylcimifugin

R

japonicum

Chang et al. (1992)

Dihydropyranochromone 170 Alsaticol

R

ostruthium

Schinkovitz et al. (2003), Vogl et al. (2011)

R

decursivum

Liu et al. (2005)

Fr

alsaticum

Skalicka-

Woźniak et al. (2009b) Phenolic acids 171 Caffeic acid

Fr, Fo

tauricum

Bartnik et al. (2003)

Fl

alsaticum

SkalickaWoźniak and Głowniak (2008)

A.p

ruthenicum

Alavi et al. (2009)

172 Neochlorogenic acid

L

japonicum

Hisamoto et al. (2003), Morioka et al. (2004)

173 Cryptochlorogeni acid

L

japonicum

Hisamoto et al. (2003)

174 Chlorogenic acid

L

japonicum

Hisamoto et al. (2003)

Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

175 Cinnamic acid

Fo

tauricum

Bartnik et al. (2003)

176 p-Coumaric acid

A.p

ruthenicum

Alavi et al. (2009)

Fr, Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

177 Ferulic acid

Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

178 Gallic acids

R

delavayi

Yan et al. (2008)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

179 Gentisic acid

Fo

tauricum

Bartnik et al. (2003)

180 p-Hydroxybenzoic

Fr, Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

181 Protocatechuic acid

Fr, Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

182 Syringic acids

Fr, Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

SkalickaWoźniak and Głowniak (2008)

183 Vanillic acid

Fr, Fo

tauricum

Bartnik et al. (2003)

Fr

alsaticum

Bartnik et al. (2003)

W.p

decursivum

Zhao et al. (2012)

Flavonoids 184 Astragalin

Fr

alsaticum

SkalickaWoźniak et al. (2011)

185 Hiperoside

Fr

alsaticum

SkalickaWoźniak et al. (2011)

186 Isorhamnetin

L, Fl,

ruthenicum

Fr L, Fl, Fr

Kuzmanov et al. (1981)

officinale

Kuzmanov et al. (1981)

L, Fl

longifolium

Kuzmanov et al. (1981)

S, L, Fl

carvifolia

Kuzmanov et al. (1981)

L, Fl,

oligophyllum

Fr 187 Kaempferol

L, Fl

Kuzmanov et al. (1981)

carvifolia

Kuzmanov et al. (1981)

L, Fl

longifolium

Kuzmanov et al. (1981)

L, Fl,

officinale

Fr L, Fl,

(1981) oligophyllum

Fr L, Fl,

Kuzmanov et al. (1981)

ruthenicum

Fr Fr

Kuzmanov et al.

Kuzmanov et al. (1981)

alsaticum

SkalickaWoźniak et al. (2011)

188 Lutein

L

sowa

Lakshminarayana et al. (2005)

189 Morin

A.p

ruthenicum

Alavi et al. (2009)

190 Quercitrin

Fl, Fr, L

ruthenicum

Kuzmanov et al. (1981)

St, Fl,

longifolium

Fr, L L, Fl, S

Kuzmanov et al., (1981)

carvifolia

Kuzmanov et al. (1981)

St, F,

officinale

Fr, L L, Fl,

(1981) oligophyllum

Fr L, Fl

Kuzmanov et al.

Kuzmanov et al. (1981)

vittijagum

Kuzmanov et al. (1981)

A.p

tauricum

Bartnik et al. (2007)

A.p

ruthenicum

Alavi et al. (2009)

Fr

alsaticum

SkalickaWoźniak et al., (2011)

Flavonoid glycoside 191 Isoquercetin

L

japonicum

Hisamoto et al. (2003)

192 Isorhamnetin-3-glucoside

Fl, Fr

officinale

Kuzmanov et al. (1981)

Fl, Fr

longifolium

Kuzmanov et al. (1981)

L, Fl

carvifolia

Kuzmanov et al.

(1981) Fl, Fr

vittijagum

Kuzmanov et al. (1981)

Fl, Fr

oligophyllum

Kuzmanov et al. (1981)

Fl, Fr

ruthenicum

Kuzmanov et al. (1981)

A.p

tauricum

Bartnik et al. (2007)

A.p

kenappii

Sarkhail et al. (2013a)

193

Isorhamnetin-3-rutinoside

A.p

ruthenicum

Bartnik et al. (2007)

A.p

tauricum

Alavi et al. (2009)

194 Quercitrin-3-rutinoside

St, L,

carvifolia

Fl, Fr St, L,

(1981) longifolium

Fl, Fr St, L,

officinale

Fl, Fr

Kuzmanov et al. (1981)

oligophyllum

Fl, Fr St, L,

Kuzmanov et al. (1981)

Fl, Fr St, L,

Kuzmanov et al.

Kuzmanov et al. (1981)

ruthenicum

Kuzmanov et al. (1981)

St, L,

195 Quercitrin-3-galactoside

vittijagum

Kuzmanov et al.

Fl, Fr

(1981)

St, L, Fl carvifolia

Kuzmanov et al. (1981)

St, Fl,

longifolium

Fr St, Fl,

(1981) oligophyllum

Fr St, L,

officinale

ruthenicum

A.p

Kuzmanov et al. (1981)

vittijagum

Fl, Fr 196 Rutin ( Rutoside)

Kuzmanov et al. (1981)

Fl, Fr St, L,

Kuzmanov et al. (1981)

Fl, Fr St, L,

Kuzmanov et al.

Kuzmanov et al. (1981)

ruthenicum

Soine et al. (1973), Alavi et al. (2009)

L

japonicum

Hisamoto et al. (2003)

A.p

tauricum

Bartnik et al. (2007)

197 Rhamnetin-3-glucoside

A.p

kenappii

Sarkhail et al. (2013a)

Phenylethanoid 198 Dillapiole

A.p

pastinacifolium

Sajjadi et al.

(2012) 199 Decursidate

R

decursivum

Kong & Yao (2000), Yao & Kong (2001)

200 1-(4-Hydroxyphenyl) ethan-

L

japonicum

1,2-diol 201 Elemicin

Hisamoto et al. (2004)

A.p

pastinacifolium

Sajjadi et al. (2012)

202 Myristicin

A.p

pastinacifolium

Sajjadi et al. (2012)

203 p-hydroxy-phenethyl

R

formosanum

Chen et al. (2008)

L

japonicum

Hisamoto et al.

ferulate 204 Salidroside

(2004) Phenylpropanoid 205 Eleutheroside B (Syringing)

R

praeruptorum

Zhang et al. (2009)

206 2-(4-Hydroxy-3-

L

japonicum

methoxyphenyl) propane-

Hisamoto et al. (2004)

1,3-diol 207 3-(2-O-β-d-Glucopyranosyl-

L

japonicum

4-hydroxyphenyl) propanoic

Hisamoto et al. (2004)

acid 208 Methyl 3-(2-O-β-dglucopyranosyl-4-

L

japonicum

Hisamoto et al., (2004)

hydroxyphenyl) propanoate 209 3-O-β-d-Glucopyranosyl-2-

L

japonicum

(4-hydroxy-3-

Hisamoto et al. (2004)

methoxyphenyl) propanol Terpenoids 210 Daucosterol

R

decursivum

Xu and Kong (2001)

R

praeruptorum

Zhang et al. (2006)

R

delavayi

Yan et al. (2008)

R

ledebourielloides

Zheng et al. (2010)

211 β-Sitosterol

R

praeruptorum

Kong et al. (1993), Zhang et al. (2005c)

R

R

medium var.

Huang et al.

gracile

(2000)

decursivum

Xu and Kong (2001)

R

delavayi

Yan et al. (2008)

R

praeruptorum

Zhang et al.

Phenanthrene-quinone 212 Tanshinone I

(2009) 213 Tanshinone II A

R

praeruptorum

Zhang et al. (2009)

Fatty acids and esters 214 Linoleic acid

L, St

graveolens

Rao and Lakshminarayana (1988)

Fl

alsaticum

SkalickaWoźniak et al. (2010)

Fl

cervaria

SkalickaWoźniak et al. (2010)

Se

chryseum

Akpinar et al. (2012)

Se

obtusifolium

Akpinar et al. (2012)

Se

palimbioides

Akpinar et al. (2012)

Se

ruthenicum

Akpinar et al. (2012)

Se

zedelmeierianum

Akpinar et al. (2012)

215 Linolenic acid

L, St

graveolens

Rao and Lakshminarayana (1988)

R

praeruptorum

Zhang et al. (2009)

Se

chryseum

Akpinar et al. (2012)

Se

obtusifolium

Akpinar et al. (2012)

Se

palimbioides

Akpinar et al. (2012)

Se

ruthenicum

Akpinar et al. (2012)

Se

zedelmeierianum

Akpinar et al. (2012)

216 Oeanolic acid

R

ledebourielloides

Zheng et al. (2010)

217 Oleic acid

Fr

alsaticum

SkalickaWoźniak et al. (2010)

Fr

cervaria

SkalickaWoźniak et al. (2010)

Se

chryseum

Akpinar et al. (2012)

Se

obtusifolium

Akpinar et al. (2012)

Se

palimbioides

Akpinar et al. (2012)

Se

ruthenicum

Akpinar et al.

(2012) Se

zedelmeierianum

Akpinar et al. (2012)

218 Palmitic acid

L, St

graveolens

Rao and Lakshminarayana (1988)

R

praeruptorum

Zhang et al. (2006)

Se

chryseum

Akpinar et al. (2012)

Se

obtusifolium

Akpinar et al. (2012)

Se

palimbioides

Akpinar et al. (2012)

Se

ruthenicum

Akpinar et al. (2012)

Se

zedelmeierianum

Akpinar et al. (2012)

219 Stearic acid

R

delavayi

Yan et al. (2008)

220 Arachidic acid-2-hydroxy-

R

ledebourielloides

Zheng et al.

glycerol ester 221 1,6-Dihydroxy-hexane-bis-

(2010) R

ledebourielloides

palmitoyl ester 222 1,2-Dipalmitoyl-3-glucosyl glycerol

Zheng et al. (2010)

R

ledebourielloides

Zheng et al. (2010)

Polyacetylene 223 Panaxynol

R

formosanum

Chen et al. (2008)

224 Acetylatractylodinol

R

praeruptorum

Chang et al. (2007)

225 Tetracosanoic

R

praeruptorum

Zhang et al. (2006)

Pyrimidines or Nucleobase 226 Uracil

L

japonicum

Hisamoto et al. (2003)

Nucleosides

L

japonicum

Hisamoto et al. (2003)

227 Guanosine

L

japonicum

Hisamoto et al. (2003)

228 Uridine

L

japonicum

Hisamoto et al. (2003)

229 Thymidine

L

japonicum

Hisamoto et al. (2003)

Amino acids 230 l -Tryptophan

L

japonicum

Hisamoto et al. (2003)

Miscellaneous 231 Adenosine

R

praeruptorum

Zhang et al. (2009)

232 Anchoic acid (Azelaic acid)

R

praeruptorum

Kong et al. (1996)

233 Butyric acid

R

praeruptorum

Zhang et al. (2009)

234 β-Carotene

L

sowa

Lakshminarayana et al. (2005)

235 Cnidioside A

L

japonicum

Hisamoto et al. (2003)

236 2,6- Dimethyl quinoline

R

praeruptorum

Zhang et al. (2006)

237 α-D-glucopyranose-1-

R

praeruptorum

hexadecanoate 238 Falcarindiol

Zhang et al. (2009)

R

praeruptorum

Miyazawa et al. (1996), Purup et al. (2009)

239 Labdanyl-3-α-ol-18-(3'"-

R

delavayi

Yan et al. (2008)

Fr

grande

Aslam et al.

methoxy-2"'-naphthyl-oate)-

(2012)

3-α-L-arabinofuranosyl-(2'->1")-alpha-Larabinofuranoside 240 (3S)-O-β-d-Glucopyranosyl-

L

japonicum

6-[3-oxo-(2S/R)-

Hisamoto et al. (2004)

butenylidenyl]-1,1,5trimethylcyclohexan-(5R)-ol (a norisoprenoid glucoside) 241 (3S)-O-β-d-Glucopyranosyl-

L

japonicum

Hisamoto et al.

6-[3-oxo-(2R)-

(2004)

butenylidenyl]-1,1,5trimethylcyclohexan-(5R)-ol (a norisoprenoid glucoside) 242 Myo-inositol

R

japonicum

Lee et al. (2004)

243 D-Mannitol

R

praeruptorum

Zhang et al.

monohexadecanoate 244 Sclerodin

(2009) R

praeruptorum

Zhang et al. (2006)

a

The plant parts have been reported by the authors in their original works.

Graphical Abstract (for review)

Ethnobotanical uses (12 species) Treatment of respiratory diseases like asthma, prostate problem, kidney and bladder ailments, as cardiac tonic and diuretic, stomachic, sedative, and antimicrobial agent.

Peucedanum genus (Apiaceae) Comprising more than 120 species

)

Literature (1970 Sep.2013 Roots and aerial parts (fruit, flower, leave, stem and seed)

Phytochemical data (near 50 species) More than 300 molecules including: coumarins and essential oils> phenolic acids> flavonoids> phenylpropanoid> hromones> fatty acids> steroids

Pharmacological data

(20 species) Focused on cardiopulmonary and neuro protection, antiinflammatory, antipyretic, antimicrobial, anti-cancer, antioxidant, antityrosinase, antiplatelet aggregation, anti-diabetic activities, and toxicity.

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Traditional uses, phytochemistry and pharmacological properties of the genus Peucedanum: a review.

The genus Peucedanum (Apiaceae) comprising more than 120 species is widely distributed in Europe, Asia and Africa. The ethnopharmacologial history of ...
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