Journal of Ethnopharmacology 157 (2014) 268–273

Contents lists available at ScienceDirect

Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep

Research Paper

Medicinal plants used for cardiovascular diseases in Navarra and their validation from Official sources M.I. Calvo a,n, R.Y. Cavero b a b

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain Department of Environmental Biology, Faculty of Sciences, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain

art ic l e i nf o

a b s t r a c t

Article history: Received 26 May 2014 Received in revised form 5 September 2014 Accepted 26 September 2014 Available online 8 October 2014

Ethnopharmacological relevance: This paper provides significant ethnopharmacological information on plants used to treat cardiovascular diseases in Navarra, Spain. Material and methods: Information was collected using semi-structured ethnobotanical interviews with 667 informants (mean age 72; 55.47% women, 44.53% men) in 265 locations. Official sources such as the European Scientific Cooperative on Phytotherapy (ESCOP), German Commission E, World Health Organization (WHO), European Medicines Agency (EMA), European Pharmacopoeia (Ph. Eur.) and Real Farmacopea Española (RFE) monographs were consulted in order to establish the therapeutic efficacy of the reported uses and to obtain further details about quality and safety aspects. A literature review was carried out on the plants that were most frequently cited and were not the subject of a monograph, using a new tool developed by the University of Navarra, UNIKA. Results: A total of 460 pharmaceutical uses were reported by the informants, belonging to 90 plant species and 39 families, mainly represented by Urticaceae, Rosaceae, Asteraceae, and Equisetaceae. The most frequently used parts of the plants were the aerial parts followed by leaves and flowers. Seventeen out of 90 plants (19%) and 208 out of 460 popular uses (45%) had already been pharmacologically validated in relation to their therapeutic efficacy and safety aspects. Conclusions: The authors propose to validate five species for their use in cardiovascular diseases: Rhamnus alaternus L., Potentilla reptans L., Equisetum telmateia Ehrh., Centaurium erythraea Rafn and Parietaria judaica L. & 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Cardiovascular Validation from Official sources Traditional knowledge Ethnopharmacology Navarra

1. Introduction Medicinal plants have been utilized as medicine throughout human history. It has been estimated that 80% of people living in developing countries are almost completely dependent on traditional medicine practices and utilize plants as drugs for their primary health care needs (Abdala et al., 2012). In this context, there is an increasing emphasis placed on proving product safety and efficacy scientifically when phytomedicines are to be used. Furthermore, the modern pharmaceutical industry is now paying more attention to medicinal plants, as scientists rediscover that they are an almost infinite source for the development of new drugs (Cavero et al., 2013). The past two decades have seen a considerable global increase in cardiovascular diseases (Tibazarwa and Damasceno, 2014). Indeed, the European Union budget for cardiovascular disease is currently estimated at €196 billion a year, with about one half of this attributed to direct healthcare costs (Nichols et al., 2012). The number of people

n

Corresponding author. Tel.: þ 34 948425600 806239; fax: þ34 948425740. E-mail address: [email protected] (M.I. Calvo).

http://dx.doi.org/10.1016/j.jep.2014.09.047 0378-8741/& 2014 Elsevier Ireland Ltd. All rights reserved.

who die from cardiovascular diseases, mainly from heart disease and stroke, will probably increase to 23.3 million by 2030 (Mathers and Loncar, 2006; WHO, 2011). Urgent investment in cardiovascular disease prevention is needed in order to improve health in European populations and to tackle the socioeconomic consequences of these diseases (Gylling et al., 2014). Previous studies carried out by our research group in Navarra have already shown that the use of many traditional medicines targeting digestive and dermatological diseases can be scientifically supported (Calvo et al., 2013; Cavero et al., 2013). The aims of the present paper are: (i) to review the medicinal plants with clinical uses that have been scientifically validated by international organizations for cardiovascular affections, and (ii) to propose plants frequently reported as being used for these diseases in different regions of the Mediterranean basin for their scientific validation, with a view to promoting their safe and effective clinical use.

2. Methodology Information was collected using semi-structured ethnobotanical interviews with 667 informants from 265 locations (Navarra,

M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 157 (2014) 268–273

Spain) following the methodology described in previous papers (Calvo et al., 2011; Cavero et al., 2011a, 2011b). In order to confirm the pharmacological validation of the uses claimed by the informants, monographs from Official International Agencies (ESCOP, Commission E, WHO and EMA) were reviewed. A literature review was carried out including all the most frequently employed plants that had not been the subject of a monograph (Calvo et al., 2013; Cavero et al., 2013). The data provided by informants were grouped into eight categories depending on the pathology in question (the exact translation of how categories were described by informants is indicated in parentheses): anemia (‘to use when the body needs iron’, ‘iron deficiency’), antihypertensive (‘to clean or purify the blood’, ‘to lower blood’, ‘to lower blood pressure’), blood circulation (‘to improve blood circulation’, ‘to stimulate blood circulation’), depurative (‘to purify or clean the body’), diuretic (‘to urinate’, to pee’, ‘if liquids are retained in the body’), heart problems (‘heart’), hemorrhoids (‘piles’) and hypercholesterolemia (‘for high cholesterol’).

3. Results and discussion A total of 460 pharmaceutical uses were reported by 667 informants, belonging to 90 plants (74% native species and 26% species introduced from other continents, or other European regions). The complete catalog of the ethnoflora of the territory surveyed is given in Akerreta (2009). The 90 medicinal plants cited belonged to 39 families, mainly represented by Urticaceae (26%), Rosaceae (17%), Asteraceae (9%), Equisetaceae (8%), Oleaceae (7%), and Rhamnaceae (4%). The most frequently used parts of the plants were the aerial parts (48%), leaves (18%), flowered aerial parts (11%), inflorescences (4%), and fruits and stems (3%). Plants were used fresh (50%), dry (23%) or either (27%), and were administered in different forms. The percentage of internal uses was 91% and the most important methods of preparation were: infusion (57%), decoction (21%), food (11%), water, olive oil or alcohol maceration and direct application (2%, each). Seventeen out of 90 plants (19%) and 208 of 460 popular uses (45%) reported in the present survey had already been pharmacologically validated in relation to their therapeutic efficacy and safety aspects for cardiovascular affections by ESCOP, Commission E, WHO and EMA Monographs (Table 1). It is important to highlight that only one of 17 plants, Aesculus hippocastanum L., had monographs in all four agencies. However, the side effects listed in the monograph of the Commission E for this plant should be taken into consideration: ‘pruritus, nausea, and gastric complaints may occur in isolated cases after oral intake’ (Blumenthal et al., 1998). Four of them had previously been reported in other studies but not yet pharmacologically validated: Calendula officinalis L., Calluna vulgaris (L.) Hull, Chamaemelum nobile (L.) All. and Prunus spinosa L. (indicated as 2b in Table 1. Since the effects claimed have not been documented, a therapeutic application cannot be recommended. Six out of 17 plants (35%) listed in Table 1 had no monograph in the European Pharmacopoeia and/or Real Farmacopea Española. The remaining 73 plants (of total 90; 81%) have been reported for cardiovascular disorders and need to be screened through standard scientific procedures to determine their action. Taking into consideration only the uses mentioned by two or more independent informants (126 uses, Table 2), the most widely treated affections are grouped into eight pathological categories: anemia (1.6%), antihypertensive (24%), blood circulation (1.6%), depurative (23%), diuretic (27%), heart problems (1.6%), hemorrhoids (18%) and hypercholesterolemia (3%).

269

The leaves of Rorippa nasturtium-aquaticum (L.) Hayek are employed for treatment of anemia defined as low red blood cell counts with clinical symptoms such as shortness of breath, lethargy and heart palpitations (Blumenthal et al., 1998). Portulaca oleraceae L. and Malus sylvestris (L.) Mill. were the only two plants cited for strengthen arteries and heart problems in general, respectively. The most widely cited plants for lowering high blood pressure were Centaurium erythraea Rafn and Rhamnus alaternus L. (30%, 9 uses of 30 total uses for this affection each), Equisetum telmateia Ehrh. and Thymus vulgaris L. (13%, 4 uses each), and Petrolesinum crispum (Mill.) Fuss and Silybum marianum (L.) Gaertner (7%, 2 uses each). It is important to highlight the importance of infusions for diuretic treatments (91%, 32 uses out of 34 total uses for this affection), Equisetum telmateia and Zea mays L. being the most cited plants (29% and 27%, respectively). Fig. 1shows that the most widely used species and their frequency of citation in the different cardiovascular problems were: Rhamus alaternus (18 uses out of 126 total uses, 14%), Potentilla reptans L. (15 uses, 12%), Equisetum telmateia (14 uses, 11%), Centaurium erythraea and Parietaria judaica L. (11 uses, 9% each). Rhamnus alaternus is an evergreen shrub of the Mediterranean climate regions known by the common name of Italian Buckthorn or Mediterranean Buckthorn. In this study, the results showed that the aerial parts are employed as antihypertensive (9 of 18 uses, 50%), depurative (7 uses, 39%), and against hypercholesterolemia (2 uses, 11%) (Fig. 1). This plant is traditionally used in different regions of Spain for cardiovascular problems: Aragon, Basque Country, Cantabria, Castile-La Mancha, Catalonia, Navarra, and Valencian Community (Akerreta, 2009, and references cited therein; Cavero et al., 2011b; Akerreta et al., 2013). We found no ethnopharmacological references in other Mediterranean areas for cardiovascular indications. Scientific studies have shown several pharmacological properties for extracts and metabolites isolated from Rhamnus alaternus. In fact, the more interesting pharmacological properties are due to the presence, amongst several different metabolites, of flavonoids (Cuoco et al., 2014), essential oils (Berka et al., 2008) and anthraquinones (Abou-Chaar et al., 1982). These compounds are secondary metabolites widely distributed in the higher plant kingdom and are known to show diverse biological and pharmacological actions. Compounds of Rhamnus alaternus have been evaluated for their in vitro antioxidant (Ammar et al., 2009), antiproliferative against human leukemia K562 cells, antimutagenic (Ammar et al., 2011), and antimicrobial (Kosalec et al., 2013) activities. The only reported application for Potentilla reptans is the treatment of hemorrhoids (15 uses, 100%), 7 uses internally in tisane for 9 days, and 8 uses externally in different forms of administration: clean with infusion, direct application, sitz baths and boiled in poultice (Table 2). Numerous ethnopharmacological studies carried out in different regions of Spain (Andalusia, Aragon, Basque Country, Cantabria, Navarra and Valencian Community) and in other Mediterranean countries (Italian Republic and Republic of Turkey) have found the same uses for the cardiovascular system (Akerreta, 2009, and references cited therein; Cavero et al., 2011a, 2011b; Calvo et al., 2011; Akerreta et al., 2013). Hemorrhoids, also called piles, are vascular structures in the anal canal which help with stool control (Schubert et al., 2009). They become pathological when swollen or inflamed (Lorenzo-Rivero, 2009). Therefore, the most appropriate pharmacological treatments for this type of affection are the use of cicatrizant and antiinflammatory agents. The most important compounds of Potentilla reptans are A-type proanthocyanidins (Okuda et al., 1992), a class of secondary phenolic metabolites, belonging to the group of tannins,

270

M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 157 (2014) 268–273

Table 1 Plants with validation from Official sources. Plant (family, voucher specimen)

Part used

Aesculus hippocastanum L. (Sapindaceae, 21119) Allium cepa L. (Liliaceae, 19324) Allium sativum L. (Liliaceae, 21718)

Seed

Maceration in alcohol for 40 days, 3 times a day for 20 days

Varicose veins (1); hemorrhoids (1)

2

1,2,3,4

Bulb

Infusion

Depurative (1)

1

3,4

Hearth problems (1); to prevent heart attacks and thrombosis (1); antihypertensive (2); hypercholesterolemia (2)

6

1,2,3

Diuretic (1); blood circulation problems (1); hemorrhoids (1)

3

2a,b

Diuretic (1)

1

2b

Inflorescence A, Infusion B

Depurative (1)

1

2b

Flowed aerial part

A, Infusion for 30 days, rest for a while and start again; B decoction; maceration in alcohol and take a few drops in water A, Decoction; infusion; maceration in anisette B A, Decoction; infusion B

Hearth problems (12); antihypertensive (15); 32 varicose veins (1); anemia (1); to improve blood circulation (1); depurative (2) Hearth problems (3); anemia (1); 6 antihypertensive (2) Antihypertensive (1); diuretic (5) 6

Leaf

A, Infusion B

Diuretic (1)

Leaf

A, Fasted infusion or decoction for 9 days B Decoction; fasted boiled food

Antihypertensive (28)

Calendula officinalis L. (Asteraceae, 18787) Calluna vulgaris (L.) Hull (Ericaceae, 21523) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Crataegus monogyna Jacq. (Rosaceae, 18723)

A, Maceration in alcohol for 40 days, and the drops are taken B consecutively (1st day: 1 drop; 2nd day: 2 drops; until 40th day: 40 drops; then gradually decreases the number of drops, from 40 to 1); fasted uncooked food Inflorescence A, Decoction; oinment with wax and olive oil B

Flowed aerial part

Sterile aerial part

Root, Stem, Branch Flowed aerial part

Leaf Aerial part Root Leaf Aerial part

Urtica urens L. (Urticaceae, 21760) Viscum album L. ssp. album (Viscaceae, 21819) Vitis vinifera L. (Vitaceae, 21809)

Popular use

Bulb

Fruit Equisetum arvense L. (Equisetaceae, 18670) Fraxinus angustifolia Vahl ssp. angustifolia (Oleaceae, 21844) Olea europaea L. (Oleaceae, 21855) Prunus spinosa L. (Rosaceae, 21969) Rosmarinus officinalis L. (Lamiaceae, 21655) Taraxacum gr. officinale Weber (Asteraceae, 21321) Urtica dioica L. (Urticaceae, 19661)

Ph Preparation and administration

Aerial part Root Aerial part, leaf Leaf

Infusion

FU Monograph

1,2,3

1a,2b,3a 2,4

1

4

28

2b,4

Antihypertensive (5); diuretic (1)

6

2a,b

A, Ointment with wax and olive oil B

Hemorrhoids (1)

1

2a,3a

A, Food: boiled or in salad; infusion or decoction for 9 days B A, Decoction; cosmestible in salad B Fasted infusion A, Infusion B A, Fasted infusion for 9 days; Boiled food for 9 day; Fasted B decoction for 7 days, resting for 30 days and start again; decoction for two intervals of 9 days with 9 days of rest between both A, Boiled food for 1 to 3 days a year B Decoction for 9 days Infusion; decoction; Maceration in water

Depurative (4); diuretic (1)

5

3a,4

Depurative (5)

5

3a,4

Antihypertensive (1) Depurative (1)

1 1

3,4a 3a,4

79

3a,4a

2

3a,4a

1 19

3,4a 4

1

4

Infusion

Depurative (70); antihypertensive (9)

Depurative (2) Depurative (1) Antihypertensive (17); hearth problems (1); depurative (1) To improve blood circulation (1)

Ph: Pharmacopeia; A: European Pharmacopoeia; B: Real Farmacopea Española; 1: ESCOP monograph; 2: German Commission E monograph; 3. WHO monograph; 4: EMA monograph. a b

Different part used. Neutral German Commission E monograph; FU: frequency of uses.

consisting of units of flavan-3-ol bound by one or two interflavan bonds. Those with twice-bonded structures, A-type, are not often found in nature, and their distribution is limited to species of Ericaceae, Sapindaceae, Lauraceae, and Rosaceae. These compounds are responsible for the astringent effects (Tomczyk and Latté, 2009). After external application, they facilitate coagulation of the proteins in the skin, which dries and hardens, and consequently they have a

protective and cicatrizing effect. On the other hand, Pilipovic et al. (2010) demonstrated the topical anti-inflammatory activity of ointments with 1% of crude water extracts of Potentilla reptans L. rhizoma and herb in croton oil model of mouse ear inflammation. This activity is mainly due to the tannin content. The sterile aerial parts of Equisetum telmateia (commonly known as Great Horsetail or Northern Giant Horsetail) have been

M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 157 (2014) 268–273

271

Table 2 Plant without validation from Official sources (mentioned by two or more independent informants). Aa

FUb

Affection

Plant (family, voucher specimen)

Part used

Anemia

Rorippa nasturtium-aquaticum (L.) Hayek (Brassicaceae, 21357)

Leaf

Internal (F)

Food (1); sirup (1)

2

Antihypertensive (lower blood pressure)

Centaurium erythraea Rafn (Gentianaceae, 21539)

Aerial part, flowered aerial part, flower Sterile aerial part

Internal (D)

Infusion, 3 times a day for 9 days (9)

9

Internal (I)

Infusion (4)

4

Aerial part

Internal (F)

Uncooked food (2)

2

Aerial part

Internal (D,F)

Decoction twice a day for 8 days (9)

9

Leaf, fruit

Internal (F)

Boiled food (2)

2

Aerial part, flowered aerial part

Internal (D)

Infusion (4)

4

Equisetum telmateia Ehrh. (Equisetaceae, 21394) Petroselinum crispum (Mill.) Fuss (Apiaceae, 22061) Rhamnus alaternus L. (Rhamnaceae, 19665) Silybum marianum (L.) Gaertner (Asteraceae, 21304) Thymus vulgaris L. (Lamiaceae, 21713)

Preparation (number of use reports)

Blood circulation (strengthen arteries)

Portulaca oleracea L. ssp. oleracea (Portulacaceae, 21911)

Aerial part

Internal (F)

Decoction (1); boiled food (1)

2

Depurative (blood purification)

Achillea millefolium L. ssp. millefolium (Asteraceae, 21175) Allium porrum L. (Liliaceae, 19976) Centaurium erythraea Rafn (Gentianaceae, 21539)

Inflorescence

Internal (I)

Infusion (1); maceration in anisette (1)

2

Stem and leaf Aerial part; flowered aerial part Sterile aerial part

Internal (F) Internal (D)

Boiled food (2) Infusion (2)

2 2

Internal (D,I)

Infusion for 9 days (2)

2

Aerial part

Internal (F,I)

Infusion (8); boiled food (1)

9

Root; Aerial part

Internal (D,F)

Fasted decoction for 9 days (7)

7

Stem; Leaf

Internal (F)

Food in salad (3)

3

Aerial part; flowered aerial part

Internal (I)

Infusion (1); decoction (1)

2

Stem Stem, leaf

Internal (F) Internal (F)

Infusion (1); boiled food (1) Infusion (2)

2 2

Sterile aerial part

Internal (D,I)

Infusion (1); decoction (2)

3

Sterile aerial part

Internal (D,F, I) Internal (I)

Infusion 3 times a day (10)

10

Infusion (2)

2

Internal (I)

Infusion (2)

2

Aerial part

Internal (F)

Infusion (3)

3

Inflorescence

Internal (D)

Infusion (2)

2

Style

Internal (D)

Infusion (8)

8

Branch, fruit

Internal (F)

Maceration in anisette (1); decoction (1)

2

External (F)

Direct application (3)

3

Equisetum ramosissimum Desf. (Equisetaceae, 21382) Parietaria judaica L. (Urticaceae, 21746) Rhamnus alaternus L. (Rhamnaceae, 19665) Rorippa nasturtium-aquaticum (L.) Hayek (Brassicaceae, 21357) Rosmarinus officinalis L. (Lamiaceae, 21658) Diuretic

Allium porrum L. (Liliaceae, 19976) Chelidonium majus L. (Papaveraceae, 21859) Equisetum ramosissimum Desf. (Equisetaceae, 21382) Equisetum telmateia Ehrh. (Equisetaceae, 21394) Filipendula ulmaria (L.) Maxim (Rosaceae, 21939) Parietaria judaica L. (Urticaceae, 21746) Petroselinum crispum (Mill.) Fuss (Apiaceae, 22061) Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (Asteraceae, 18775) Zea mays L. (Poaceae, 21014)

Flowered aerial part Aerial part

Heart problem

Malus sylvestris (L.) Mill. (Rosaceae, 21940)

Hemorrhoids

Chelidonium majus L. (Papaveraceae, Stem, leaf, latex 21859) Potentilla reptans L. (Rosaceae, 18795) Rhizome, whole plant, aerial part, leaf Sedum sp. (Crassulaceae, 21342) Aerial part Verbascum sinuatum L. Root, whole plant, (Scrophulariaceae, 22013) leaf

Hypercholesterolemia Rhamnus alaternus L. (Rhamnaceae, 19665) Urtica dioica L (Urticaceae, 21747) a b

A: administration; F: fresh; D: dry; I: without distinction. FU: frequency of uses.

Internal (F,D); Fasted infusion or decoction for 9 days (7); clean with infusion 15 External (D,F) (3); direct application (2); sitz baths (2); boiled in poultice (1) External (F) Roasted direct application (2) External (F,D) Clean with decoction (2); boiled in poultice (1)

2 3

Aerial part

Internal (F)

Infusion (2)

2

Aerial part

Internal (F,I)

Infusion (2)

2

272

M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 157 (2014) 268–273

Fig. 1. The most used species and their frequency of use in the different cardiovascular diseases.

reported to lower blood pressure (4 of 14 uses, 29%) and have diuretic properties (10 uses, 71%). In both cases the administration form is infusion. In reference to ethnopharmacological studies of this plant, it is interesting to point out that the distribution of its use is the same as Potentilla reptans: Andalusia, Aragon, Basque Country, Cantabria, Castile-La Mancha, Catalonia, Navarra, and Region of Murcia in Spain, and Italian Republic and Republic of Turkey (Akerreta, 2009, and references cited therein; Akerreta et al., 2013). The number of scientific references about the composition of Equisetum telmateia are few; it contains essential oils (Fons et al., 2013), various flavonoids and their glycosides, phenolic acid derivates and flavan-3-ol compounds (Correia et al., 2005) with possible antioxidant and medicinal properties. Medicinal plants belonging to the genus Equisetum are very often used in traditional medicine. They are highly efficient in treating urinary tract infection, cardiovascular diseases, respiratory tract infection and medical skin conditions. Equisetum arvense L. is one of the most common species of this genus (Willfort, 1997). It has been traditionally described as a diuretic in European Pharmacopeias, German Commission E expert panel and EMA (Table 1). The taxonomic proximity between the two species, Equisetum telmateia and Equisetum arvense, suggests that the chemical composition and pharmacological action should also be very similar. Centaurium erythraea (commonly known as Common or Small Centaury) has been reported to lower blood pressure (9 of 11 uses, 82%) and act as a depurative (2 uses, 18%); in both cases the administration form is infusion. It is a plant widely used in traditional medicine, Spain (Andalusia, Basque Country, Cantabria, Castile-La Mancha, Catalonia, Navarra, Principality of Asturias), Greece, Italian Republic, Kingdom of Morocco, and Portuguese Republic (Akerreta, 2009, and references cited therein; Cavero et al., 2011a; Akerreta et al., 2013). Centaurium erythraea is a widely distributed herbaceous plant which is renowned for its bitter properties. The bitter taste is due to the secoiridoids (Aberham et al., 2011). Secoiridoid glucosides, swertiamarin and sweroside are reported in numerous applications for digestive problems, e.g. in mild dyspeptic/gastrointestinal disorders, and/or in temporary loss of appetite (EMA, 2009), as well as being useful as a cholagogue, hepatoprotective (Mroueh et al., 2004), and gastroprotective agent (Tuluce et al., 2011). Many scientific articles about Centaurium erythraea have confirmed its pharmacological activities as an antioxidant (Siler et al.,

2014), antimicrobial (Kirbag et al., 2009; Siler et al., 2014), and antidiabetic (Hamza et al., 2010); and the correlation between these properties and its phytochemical composition including alkaloids (Sarker et al., 2001), essential oils (Jovanovic et al., 2009), coumarins (Valentao et al., 2003), triterpenes (Bellavista et al., 1974) and xanthone derivatives (Valentao et al., 2002). In relation to cardiovascular affections, Haloui et al. (2000) showed that Centaurium erythraea administered at the dose of 8% had significant effects on urinary excretion of water and electrolytes, which supports the claims in the traditional medicine of Navarra that this plant has diuretic efficacy. The weed Parietaria judaica (common name Spreading Pellitory or Pellitory of the wall), is one of the most important pollen allergen sources in the Mediterranean area. For this reason there are numerous scientific articles related to the topic (AbelFernandez et al., 2012). However, this plant has also been employed for cardiovascular problems in traditional medicine in several countries, Spain (Andalusia, Aragon, Canary Islands, Castile-La Mancha, Catalonia, Navarra, Region of Murcia, and Valencian Community); Italian Republic; and Portuguese Republic (Akerreta, 2009, and references cited therein; Cavero et al., 2011a, 2011b; Akerreta et al., 2013). In our study, the aerial parts of Parietaria judaica were reported to be used as a depurative (9 out of 11 uses, 82%) and a diuretic (2 uses, 18%). In both cases the main administration form was infusion. Despite the high number of ethnopharmacological studies listed above, no scientific references were found to establish a correlation between the plant's chemical composition and the pharmacological actions reported in the cardiovascular system.

4. Concluding remarks Nineteen percent of the medicinal plants used in Navarra for cardiovascular problems were pharmacologically validated in relation to their therapeutic efficacy and safety aspects by official international organisms. The authors highlight five species out of the remaining 81% for future validation (Rhamnus alaternus, Potentilla reptans, Equisetum telmateia, Centaurium erythraea, and Parietaria judaica). Numerous ethnobotanical, phytochemical and pharmacological studies suggest that these medicinal plants have proved to be effective for prevention and cure of cardiovascular disorders and could be used after validation, possibly leading to relatively inexpensive, effective, and safe therapies. References Abdala, S., Martín-Herrera, D., Benjumea, D., Gutiérrez, S.D., 2012. Diuretic activity of some Smilax canariensis fractions. Journal of Ethnopharmacology 140, 277–281. Abel-Fernandez, E., Fernandez-Caldas, E., Cases, B., Tudela, J., Ferrer, A., Guardia, P., Casanovas, M., Subiza, J., 2012. Allergenic potency of Parietaria judaica and Olea europaea using different serum pools containing, or not specific IgE to the major allergens. Allergy 67, 540 (540). Aberham, A., Pieri, V., Croom, E.M., Ellmerer, E., Stuppner, H., 2011. Analysis of iridoids, secoiridoids and xanthones in Centaurium erythraea, Frasera caroliniensis and Gentiana lutea using LC-MS and RP-HPLC. Journal of Pharmaceutical and Biomedical Analysis 54, 517–525. Abou-Chaar, C.I., Kabbara, R.A., Shamlian, S., 1982. A chromatographic study of the anthraquinones of Rhamnus alaternus L. III. extraction, isolation and chromatographic characterization of the anthraglycosides of the stem bark. Pharmaceutical Biology 20, 13–18. Akerreta, S., 2009. Etnobotánica farmacéutica en Navarra: del uso tradicional de las plantas medicinales a su evidencia científica (Ph.D. thesis). Faculty of Science, University of Navarra p. 831 (1 CD), Pamplona, Spain. Akerreta, S., Calvo, M.I., Cavero, R.Y., 2013. Sabiduría popular y plantas curativas. Ediciones i (Integralia la casa natural, S.L.). Madrid. Ammar, R.B., Neffati, A., Skandrani, I., Sghaier, M.B., Bhouri, W., Ghedira, K., Chekir-Ghedira, L., 2011. Anti-lipid peroxidation and induction of apoptosis in the erythroleukaemic cell line K562 by extracts from (Tunisian) Rhamnus alaternus L. (Rhamnaceae). Natural Product Research 25, 1047–1058.

M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 157 (2014) 268–273

Ammar, R.B., Bhouri, W., Sghaier, M.B., Boubaker, J., Skandrani, I., Neffati, A., Bouhlel, I., Kilani, S., Mariotte, A.M., Chekir-Ghedira, L., Dijoux-Franca, M.G., Ghedira, K., 2009. Antioxidant and free radical-scavenging properties of three flavonoids isolated from the leaves of Rhamnus alaternus L. (Rhamnaceae): a structure-activity relationship study. Food Chemistry 116, 258–264. Bellavista, V., Schiafella, F., Mezzetti, T., 1974. Triterpenoids of Centaurium erythraea. Phytochemistry 13, 289–290. Berka, B., Hassani, A., Allaf, K., Chemat, F., 2008. Analysis by gas chromatographymass spectrometry of the essential oil of Rhamnus alaternus L. (Rhamnaceae), an aromatic and medicinal plant growing in algeria. Journal of Essential Oil Bearing Plants 11, 563–570. Blumenthal, M., Busse, W.R., Goldberg, A., Gruenwald, J., Hall, T., Klein, S., 1998. The Complete German Comission E Monographs. American Botanical Council, Boston. Calvo, M.I., Akerreta, S., Cavero, R.Y., 2013. The pharmacological validation of medicinal plants used for digestive problems in Navarra, Spain. European Journal of Integrative Medicine 5, 537–546. Calvo, M.I., Akerreta, S., Cavero, R.Y., 2011. Pharmaceutical ethnobotany in the riverside of Navarra (Iberian Peninsula). Journal of Ethnopharmacology 135, 22–33. Cavero, R.Y., Akerreta, S., Calvo, M.I., 2013. Medicinal plants used for dermatological affections in Navarra and their pharmacological validation. Journal of Ethnopharmacology 149, 533–542. Cavero, R.Y., Akerreta, S., Calvo, M.I., 2011a. Pharmaceutical ethnobotany in Northern Navarra (Iberian Peninsula). Journal of Ethnopharmacology 133, 138–146. Cavero, R.Y., Akerreta, S., Calvo, M.I., 2011b. Pharmaceutical ethnobotany in the Middle Navarra (Iberian Peninsula). Journal of Ethnopharmacology 137, 844–855. Correia, H., González-Paramás, A., Amaral, M.T., Santos-Buelga, C., Batista, M.T., 2005. Characterisation of polyphenols by HPLC-PAD-ESI/MS and antioxidant activity in Equisetum telmateia. Phytochemical Analysis 16, 380–387. Cuoco, G., Mathe, C., Vieillescazes, C., 2014. Liquid chromatographic analysis of flavonol compounds in green fruits of three Rhamnus species used in Stil de grain. Microchemical Journal 115, 130–137. European Medicines Agency (EMA), Assessment report on Centaurium erythraea Rafn. s.l. including C. majus (H. et L.) Zeltner and C. Suffruticosum (Griseb.) Ronn., herba, for the development of a community herbal monograph, Doc. Ref.: EMA/HMPC/105535/2008, 2009. Fons, F., Froissard, D., Bessiere, J.M., Fruchier, A., Buatois, B., Rapior, S., 2013. Volatile composition of six horsetails: prospects and perspectives. Natural Product Communications 8, 509–512. Gylling, H., Plat, J., Turley, S., Ginsberg, H.N., Ellegård, L., Jessup, W., Jones, P.J., Lütjohann, D., Maerz, W., Masana, L., Silbernagel, G., Staels, B., Borén, J., Catapano, A.L., De Backer, G., Deanfield, J., Descamps, O.S., Kovanen, P.T., Riccardi, G., Tokgözoglu, L., Chapman, M.J., for the European Atherosclerosis Society Consensus Panel on Phytosterols Journal, 2014. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis 232, 346–360. Haloui, M., Louedec, L., Michel, J.B., Lyoussi, B., 2000. Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea. Journal of Ethnopharmacology 71, 465–472. Hamza, N., Berke, B., Cheze, C., Agli, A.N., Robinson, P., Gin, H., Moore, N., 2010. Prevention of type 2 diabetes induced by high fat diet in the C57BL/6J mouse by two medicinal plants used in traditional treatment of diabetes in the east of Algeria. Journal of Ethnopharmacology 128, 513–518.

273

Jovanovic, O., Radulovic, N., Stojanovic, G., Palic, R., Zlatkovic, B., Gudzic, B., 2009. Chemical composition of the essential oil of Centaurium erythraea Rafn (Gentianaceae) from Serbia. Journal of Essential Oil Research 21, 317–322. Kirbag, S., Zengin, F., Kursat, M., 2009. Antimicrobial activities of extracts of some plants. Pakistan Journal of Botany 41, 2067–2070. Kosalec, I., Kremer, D., Locatelli, M., Epifano, F., Genovese, S., Carlucci, G., Randić, M., Zovko, K.M., 2013. Anthraquinone profile, antioxidant and antimicrobial activity of bark extracts of Rhamnus alaternus, R. fallax, Radiacmea intermedia and Rhynchostegiella pumila. Food Chemistry 136, 335–341. Lorenzo-Rivero, S., 2009. Hemorrhoids: diagnosis and current management. American Journal of Surgery 75, 635–642. Mathers, C.D., Loncar, D., 2006. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine 3, e442. Mroueh, M., Saab, Y., Rizkallah, R., 2004. Hepatoprotective activity of Centaurium erythraea on acetaminophen-induced hepatotoxicity in rats. Phytotherapy Research 18, 431–433. Nichols, M., Townsend, N., Luengo-Fernandez, R, et al., 2012. European Cardiovascular Disease Statistics 2012. European Heart Network, European Society of Cardiology, Brussels/Sophia Antipolis. Okuda, T., Yoshida, T., Hatano, T., Iwasaki, M., Kubo, M., Orime, T., Yoshizaki, M., Naruhashi, N., 1992. Hydrolysable tannins as chemotaxonomic markers in the Rosaceae. Phytochemistry 31, 3091–3096. Pilipovic, S., Mulabegovic, N., Kovac-Besovic, E., Mornjakovic, Z., Uzunovic, A., Elezovic, A., Hadzidedic, S., 2010. Topical anti-inflammatory activity of ointments with 1% of crude water extracts of rhizoma and herb Potentilla reptans L. in croton oil model of mouse ear inflammation. Planta Medica 76, 1244 (1244). Sarker, S.D., Laird, A., Nahar, L., Kumarasamy, Y., Jaspars, M., 2001. Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae). Phytochemistry 57, 1273–1276. Schubert, M.C., Sridhar, S., Schade, R.R., Wexner, S.D., 2009. What every gastroenterologist needs to know about common anorectal disorders. World Journal of Gastroenterology 15, 3201–3209. Siler, B., Zivkovic, S., Banjanac, T., Cvetkovic, J., Zivkovic, J.N., Ciric, A., Sokovic, M., Misic, D., 2014. Centauries as underestimated food additives: antioxidant and antimicrobial potential. Food Chemistry 147, 367–376. Tibazarwa, K.B., Damasceno, A.A., 2014. Hypertension in developing countries. Canadian Journal of Cardiology 30, 527–533. Tomczyk, K.P., Latté, M., 2009. Potentilla – a review of its phytochemical and pharmacological profile. Journal of Ethnopharmacology 122, 184–204. Tuluce, Y., Ozkol, H., Koyuncu, I., Ine, H., 2011. Gastroprotective effect of small centaury (Centaurium erythraea L.) on aspirin-induced gastric damage in rats. Toxicology and Industrial Health 27, 760–768. Valentao, P., Andrade, P.B., Silva, A.M.S., Moreira, M.M., Seabra, R.M., 2003. Isolation and structural elucidation of 5-formyl-2,3-dihydroisocoumarin from Centaurium erythraea aerial parts. Natural Product Research 17, 361–364. Valentao, P., Andrade, P.B., Silva, E., Vicente, A., Santos, H., Bastos, M.L., Seabra, R.M., 2002. Methoxylated xanthones in the quality control of small centaury (Centaurium erythraea) flowering tops. Journal of Agricultural and Food Chemistry 50, 460–463. WHO, 2011. Global Status Report on Noncommunicable Diseases 2010. World Health Organization, Geneva. Willfort, R., 1997. Gesundheit durch Heilkräuter: Erkennung, Wirkung und Anwendung der wichtigsten einheimischen Heilpflanzen, 27. Verlag Trauner, Linz, Austria.