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Review

Journal of Pharmacy And Pharmacology

A review on ethnobotany, phytochemistry and pharmacology of plant genus Caralluma R. Br. Muhammad Adnana, Saleem Janb, Sakina Mussarata, Akash Tariqa, Shaheen Begumc, Anila Afroza and Zabta Khan Shinwarid a Department of Botany, Kohat University of Science and Technology, Kohat, bDepartment of Chemistry, University of Science and Technology Bannu, Bannu, cDepartment of Environmental Sciences, Fatima Jinnah Women University, Punjab, dDepartment of Biotechnology and Bioinformatics, Quaid-i-Azam University Islamabad, Islamabad, Pakistan

Keywords Apocynaceae; chemical compounds; conservation; ethnopharmacology; toxicology Correspondence Muhammad Adnan, Department of Botany, Kohat University of Science and Technology, 26000 Kohat, Pakistan. E-mail: [email protected] Received January 15, 2014 Accepted March 16, 2014 doi: 10.1111/jphp.12265

Abstract Objectives Caralluma is a xerophytic genus used as traditional medicine for the treatment of diabetes, inflammation, leprosy, obesity and rheumatism. Objectives of this review are to establish a relationship between traditional uses and scientific studies by critically evaluating the available fragmented literature on ethnobotany, pharmacology, phytochemistry and toxicology of genus Caralluma. Key findings Ethnomedical uses of Caralluma have been recorded from various countries such as China, India, Iran and Pakistan for six major classes of diseases including diabetes and gastrointestinal disorders. This review indicated the efficacy of genus Caralluma in several in vitro and in vivo pharmacological properties such as antimicrobial, antioxidant and anticancer activity. These bioactivity might be due to the presence of certain classes of compounds in genus Caralluma including pregnane glycosides, flavonoid glycosides and flavones. Summary Traditional uses and scientific evaluation of Caralluma indicates that it is one of the most widely used genus in some parts of the world. Further studies on the structural activity relationship of some of the isolated compound may improve their biological potency as well as scientific exploitation of traditional uses of the genus.

Introduction Caralluma R. Br. (family Apocynaceae) is a xerophytic genus of 120 species. The etymology of ‘Caralluma’ is derived from the Arabian word, ‘qarh al-luhum’, meaning wound in the flesh or abscess. Caralluma is also regarded as the synonym of genus Boucerosia; however, the only difference between the two genera is the arrangement of floral parts.[1] Plant species belonging to the genus Caralluma have normally small caducous leaves. Mostly, they are succulent perennial herbs, some of which are reported as edible species.[2] Various medicinal uses of Caralluma species have been documented in the Arabic and Indian traditional medicine including treatment of diabetes, cancer, tuberculosis, snake and scorpion bites, skin rashes, scabies, fever, and inflammation.[3–6] Most common uses of this genus have been recorded as a famine food without any reported adverse effects till date.

Several species of the genus Caralluma are rich in pregnane glycosides, flavone and megastigmane glycosides, and various esters, which authenticate its medicinal importance.[7–9] Antioxidant, anticancer, antidiabetic, antiinflamatory, antimicrobial, anti-eczemic, antimalarial and antifungal properties of various Caralluma extracts showed its pharmacological importance.[10,11] It is also worth mentioning that C. tuberculata and C. edulis were previously cited as Boucerosia tuberculata and B. edulis in Pakistan, which were later identified as Caralluma spp.[1,12] Species like C. tuberculata, C. fimbriata and C.attenuata are the most popular, widely utilized and highly investigated species in the genus despite of relatively high number of other species in the genus, which are more or less unexplored. The aim of this review is to establish a relationship between traditional uses and scientific studies through

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

1

Medicinal properties of genus Caralluma

Muhammad Adnan et al.

critical evaluation of the available fragmented literature on ethnobotany, pharmacology, phytochemistry and toxicology of genus Caralluma. Further, this review will highlight the importance of Caralluma and will provide baseline for future research studies.

Methodology Published papers were retrived from three online bibliographical databases: Google Scholar, ISI Web of Knowledge and ScienceDirect Navigator. There were more than 900 published literatures on genus Caralluma. We did not include literature related to molecular, physiological and anatomical aspects of genus Caralluma. Therefore, we selected about 400 potentially interesting articles and other literature related to the geographical distribution, taxonomy, morphology, trade and conservation status, ethnobotany, phytochemistry, pharmacology and toxicity of plant genus Caralluma. We reviewed the reference lists of about 117 of the selected literature having more detailed, comprehensive and accurate information. Data were organized and tabulated by using Microsoft Excel and Microsoft Word. Ethnobotanical table consists of species name, part used, location, medicinal uses and recipes (Table 1). Data on phytochemistry and pharmacological activity of reported Caralluma species comprises species names, chemical constituents extracted and types of pharmacological activity performed so far (Table 2).

Plant description Geographical distribution Genus Caralluma is widely distributed in Africa, Asia (Afghanistan, India, Pakistan, Sri Lanka and Iran), Arabian Peninsula, South Africa, Southeast Europe and Canary Islands.[74,75] About 12 species and 7 varieties of Caralluma existed in India, of which 11 species are endemic to south India[76] (Figure 1). Many of these species are rare and endangered including C. bhupenderiana and C. sarkariae. In Pakistan, two species have been recognized as C. tuberculata and C. edulis,[77] which occurs in the semiarid regions and being used as emergency food.[78] The locations cited in the ‘flora of Pakistan’ for the collection of C. tuberculata are Waziristan, Kurram valley, up to 4000 ft in Peshawar Hills and salt range (saline areas) of Punjab province.[12]

Taxanomy and morphology Genus Caralluma belongs to superorder Gentiananae, order Gentianales, class Magnoliopsida and subclass Asteridae.[5] Previously, genus Caralluma belonged to the family Asclepiadaceae, which is also known as milkweed family.[79] 2

No. of studies

Species

50 45 40 35 30 25 20 15 10 5 0 India

Pakistan Saudia Arabia

Italy

Spain

Nigeria

Figure 1 Number of Caralluma species and their scientific studies in different countries.

Asclepiadaceae comprised of about 200 genera and 2500 species.[80] However, modern molecular and genetic studies have suggested Asclepiadaceae to be treated as a subfamily Asclepiadoideae in the family Apocynaceae. Morphologically Caralluma plants are erect, creeping and scrambling. Their stems are succulent, showing tetragonal branches and dentate along the margin with soft spines in the notches.[75] They are herbs of approximately 15–45 cm up to 1 m in height with subtrete stem having grooves. The spines that cover the angled stem are actually leaves. The star-shaped fleshy flowers of these plants produce worst smell of all succulent plants. Ordinarily, the plants grows in late summer, the foul-smelling blossoms are usually purple, black, yellow, maroon, red or dark brown, respectively. Their height of blossoms ranges from 0.5 to 2 inches or more across and born at the base of plant in the wild. These blossoms are pollinated by flies that are greatly attracted to the plant. The flowers are in umbel shape and have various dark colours.[81] Calyx is 5-partite, with ovate to linear-lanceolate lobes. Corolla is purple or yellowish with purple streaks, rotate or broadly campanulate, five-lobed and valvate in bud. Corona is double and attached to the stamina column. The outer corona is of five segments each split into two parts, while the inner corona is of five linear segments incumbent on the anthers. Staminal column is short, arising from the base of the corolla; anthers are lacking appendages. Pollen mass is one in each anther cell, with a pellucid margin.[79] Fruits are long narrow, linear, erect and smooth with pointed apex, in bilocular.[3] Caralluma species perform crassulacean acid metabolism (CAM) for survival in their natural habitat. The studies in this regard indicated that Caralluma species exhibited low values of stomatal density, stomatal size and stomatal pore size area of stem, respectively. These stomatal features have repeatedly been recognized as characteristic of plants exhibiting the CAM pathway.

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

Whole plant Stem

India,Spain

India

India

India

Saudi arabia

India

Saudi Arabia Saudi Arabia India

India,Iran

C. attenuate

C. laciantha

C. stalagmifera

C. adscendens

C. sinaica (Decne.)

C. diffusa (Wight) N.E.Br C. penicillata C. russeliana C. bhupenderiana Sarkaria C. fimbriata

Italy

Medicinal

Whole plant

India

C. umbellata

C. europaea N.E.Br.

Organogenesis, medicinal uses Antitrypanosomal

Whole plant

Iran, Pakistan

Stem and fruits

Leaves

Stem

Stem

Stem

Whole plant

Root

Whole plant

Pharmaceutical

Obesity, waist decrease, blood purification, malnutrition, blood cholesterol level

Hypoglycaemic

Paralysis, rheumatism, malnutrition

Burning wounds, malnutrition

Diabetes, migraine, anticancer Wounds, ethnoveterinary uses

Parasitic diseases, Alzheimer, rheumatism, hypertension, gastric problems, antidiabetic, febrifuge, gastric, leprosy Ulcer, abdominal pain

Kidney pain

C. edulis Benth.

Leaves

Iran

Disease category

C. oxyacantha

Part used

Geographical distribution

Ethnobotany of genus Caralluma

Species

Table 1

Cut into pieces and mixed with table salt, kept for half an hour to remove the bitter juices, washed with cold water three times, cooked as a vegetable. Eaten as a salad for blood purification and weight loss. Extract available as GENASLIM (capsules) for body weight control.

The plant is simply chewed by diabetic patient to lower glucose level. Chemical extracts

Burnt in direct fire and eaten for 5 days regularly at empty stomach for ulcer treatment. It is eaten raw for diabetics. Plant juice taken along with black paper is recommended in migraine. Two stem pieces of plant, little lime and cherry are crushed together and applied on affected part for 4 days. Two handfuls of Mimosa pudica, 0.5 kg C. laciantha, one spoon Curcuma langa and little lime juice are mixed and applied on affected part for 7 days. Stem of C. stalagmiferaand leaves of Azadirachta indica are crushed, mixed with oil and applied on affected areas. Plant juice is mixed with coconut oil, heated for 5 min and applied on the affected parts.

Leaves are taken along honey for reducing kidney pain. Cooked as vegetable, considered nutritive and used for the treatment of rheumatism and diabetes mellitus.

Ethnomedicinal recipes

Zito et al. 2010[30]

Kamalakkannan et al. 2010[28] Naik et al. 2012[21] Lawrence and Choudary 2004[29]

Naik et al. 2012[21] Gowri and Chinnaswamy 2011.[22] Nawal et al. 2012[23] Habibudin et al. 2008[24] Karthik et al. 2003[25] Ramadevi et al. 2012[26] Sattar et al. 2009[3] Sattar et al. 2009[3] Ugraiah et al. 2011[27]

Naik et al. 2012[21]

Kishore et al. 2010[17] Karuppusamy 2007[18] Kumar et al. 2011[19] Sattar et al. 2008[20] Naik et al. 2012[21]

Mahmood et al. 2011[14] Ali et al. 2011[15] Ahmad et al. 2009[16]

Safa et al. 2013[13]

Citations

Muhammad Adnan et al. Medicinal properties of genus Caralluma

3

4

C. tuberculata N. E. Brown

Whole plant Whole plant

Iran, India, Pakistan, Nigeria, Saudi Arabia

Whole plant

Whole plant

India UAE

C. bhupenderiana C. arabica N.E.Brown

Above-ground parts

Muscat, Oman

Egypt

C. wissmannii

Stem

India

C. nilagiriana

Part used

India

Spain, Africa Nigeria

C. negevensis C. diazielli

C. pauciflora (Wight) N.B.Br. C. quadrangular

Geographical distribution

Continued

Species

Table 1

Vegetable, jaundice, dysentery, stomach pain, constipation, hepatitis B and C, freckles and pimples, blood purification, diabetes, liver ailments, rheumatism, tonic, febrifuge, gastric problems, hypertension, inflammation, paralysis, anticancer

Vegetable, tonic, wound healing antioxidant activity

Ethnoveternary uses Vegetable, nutritive and tonic, liver diseases, diabetes, hypertension, cuts, wounds, burns and itchy skin Nutritive, energy source

Anticancer, lung diseases Cardiovascular, diabetes, blood cholesterol level Antimicrobial, infectious diseases Medicinal

Disease category

The entire plant is edible. The juice from its stem is added to fresh milk as a general tonic. Whole plant is dried, powdered and taken with water. Fresh plant is directly eaten by diabetic patient and is very effective. Cooked as a vegetable. Whole plant is pounded and drinks in the form of tea to cure liver ailments, high blood pressure and diabetes. Fresh plant is chewed for freckles, pimples and for blood purification.

Cooked as vegetable also eaten as salad.

Cooked as vegetable food. Crushed flowers applied externally for wounds and cuts. Juice of stem used to curdle milk and given to sick to speed convalescence.

Chloroform extract of the plant is used, which have antibacterial activity. Petroleum ether extracts are and used as for medicinal purposes

Plant extract is used as required.

Ethnomedicinal recipes

Safa et al. 2013[13] Tareen et al. 2010[36] Shah et al. 2012, 2013[35,89] Manzoor et al. 2013[37] Ahmad et al. 2009[16] Marwat et al. 2008[38] Mahmood et al. 2011[14] Mahmood et al. 2010[39] Rauf et al. 2013[11] Zabihullah 2006[40]

Shah et al. 2012[35]

Ugraiah et al. 2011[27]

Ugraiah et al. 2011[27] Zakaria et al. 2001[34]

Prabakaran and Kalimuthu 2013[32] Dawidar et al. 2012[33]

Braca et al. 2002[8] Tanko et al. 2013[31]

Citations

Medicinal properties of genus Caralluma Muhammad Adnan et al.

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

Part investigated

Whole plant

Whole plant

Whole plant

Whole plant

Above-ground parts

Whole plant

Above-ground parts

C. umbellata

C. tuberculata

C. adscendens

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

C. negevensis

C. arabica

C. lasiantha

C. penicillata

Saudi arabia

India

UAE

Jordan

India

Pakistan, Saudi arabia

India

Place/ Country

Caralasigenin 3-O-β-D-glucopyranosyl(1→4)-β-D-digitalopyranoside-20-O-α-L-rhamnosyl (1→6)-β-D-glucopyranoside Caralumagenin 3-O-β-D-glucopyranosyl(1→4)-β-D-digitalopyranoside-20-O-α-L-rhamnosyl (1→6)-β-D-glucopyranoside Luteolin neohesperidoside Three C-15 oxypregnane glycosides, penicillosides A–C Penicillosides

Carumbelloside-III, Carumbelloside-VI, Boucergenin, Umbelloside I, Umbelloside III, Umbelloside IV 3-O-β-D-gluco- pyranosyl-(1→6)-β-D-glucopyranosyl-3β,14β-dihydroxypregn-5-en-20-one 3-O-β-D-glucopyranosyl-3β,14β- dihydroxypregn-5-en-20-one Carumbelloside-I (3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl-3β,14β-dihydroxypregn-5en-20-one) 3β-hydroxy-pregn-5-ene(CRURI)and 3β,14β-dihydroxypregn-5-ene (CRURII) 3-O-β-D-glucopyronosyl,8β-isopropoxy,14β-ethynyl,pregn-5en-21,21-dimethy16,17 lactone Caralumagenin3-O-β-D-glucopyranosyl(1→4)–D-digitalopyranoside-20-O-β-D-glucopyranoside Caralumagenin3-O-β-D-glucopyranosy(1→ 4)-β-D-digitalopyranoside-20-O-(2-O-bengoyl)-β-Dglucopyranoside Caralumagenin3-O-(6-O-benzoyl-β-D-glucopyranosyl(1→4))-β-D-digitalopyranoside-20-O-(2-Obenzoyl)-β-D-glucopyranoside Ethanol, vitamin, phenolic content,carbohydrate,protein (Three flavone glycosides) Luteolin-4′-O-β-D-glucopyranosyl(2→1)-α-L-rhamnopyranoside Kaempferol-7-O-β-D-glycopyranosyl (2→1)-α-L- rhamnopyranoside Kaempferol-3-O-β-D-glycopynnaryl (6→1)-α-L-rahmnopyranoside 3-O-β-D- glucopyranosyl-(1→4)-β-D-(3-0-methyl-6desoxy)-galactopyranosyl)-14-hydroxy14β-pregnane-20-one 3-O-(β-D-glucopyranosy1-(1→4)-β-D-(3-0-methyl-6desoxygalactopyranosy1)-14 20dihydroxy-14β-pregnane Caratubersides Steroids,terpenoids,reducingsugars,tannins,betacyaninand amino acid Methanol, aqueous, petroleum ether extract, n-butanol, ether, petroleum 12β,20-O-dibenzoyl-5α,6-dihydrosarcostin β-oleandropyranosyl-(1→4)-βcymaropyranosyl-(1→4)-β-digitoxypyranosyl-(1→4)-β-cymaropyranosyl-(1→4)-βcymaropyranoside (1) 12β-O-benzoyl-3β,11α,14β,20R-pentahydroxy-pregn-5-ene(2) 11α-O-benzoyl-3β,12β,14β,20R-pentahydroxy-pregn-5-ene (3), (9R)-2β,9-dihydroxymegastigma-4,7-dien-3-one-9-O-α-L-rhamnopyranosyl-(1→6)-β-Dglucopyranoside 2β,9-dihydroxymegastigma-4-en-3-one-9-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside luteolin 3/-O-β-D-glucopyranoside-4′-O-α-lrhamnopyranosyl-(1→2)-β-D-glucopyranoside luteolin 3′,4′-di-O-β-D-glucopyranoside 20 pregnane glycosides Ethanolic extract

Compound Isolated

Phytochemical and pharmacological investigation of genus Caralluma

Caralluma spp.

Table 2

Antinociceptive, anti-inflamatory

Cytotoxic, genotoxic

Antioxidant, antidiabetic, antibacterial, antimicrobial, appetite suppressing, hypolipidaemic

Anti-inflamatory, analgesic, cytotoxic, scavanging, antimalarial, antitrypanosomal, antioxidant, antifungal

Anti-inflamatory, hypoglycaemic, antimicrobial, antioxidant, hypocholesterolaemic, pesticide, anti-androgenic, hemolytic 5-alpha reductase inhibitor, anticancer, anti-eczemic, anti-acane, anti-androgenic, anti-arthritic, anticoronary, insectifuge, antinociceptive

Reported Activity

Sattar et al. 2001, 2009[3,9]

Qiu et al. 1999[47]

Zakaria et al. 2001[34]

Tatiya et al. 2010[55] Kulkarni et al. 2012[56] Reddy et al. 2011[57] Hadadare and Salankhe 2013[58] Maheshu et al. 2012[59] Sakore et al. 2012[60] Badar et al. 2003[7] Braca et al. 2002[8]

Ahmed et al. 1992[48] Waheed et al. 2011[10] Rizwani et al. 1990[49] Khattak 2011[50] Al-Bekairi et al. 1992[51] Al-Harbi et al. 1994[52] Sattar et al. 2008, 2009[3,20] Ahmad et al. 1988[53] Khan et al. 2013[54] Rauf et al. 2013[11]

Ray et al. 2011[41] Kunert et al. 2009[42] Jeyakumar et al. 2013[43] Lin et al. 1994[44] Ramesh et al. 1998[45] Kishore et al. 2010[17] Kalyani et al. 2013[46] Qiu et al. 1997[47]

References

Muhammad Adnan et al. Medicinal properties of genus Caralluma

5

6

Above-ground parts

Fresh leaves, above-ground parts

C. retrospiciens

C. wissmannii

Whole plant

C. attenuate

Above-ground parts

Whole plant

C. quadrangula

C. russeliana

Part investigated

Continued

Caralluma spp.

Table 2

Yemen

Saudi Arabia

Sudon

India

Saudi arabia

Place/ Country 12,20-di-O-benzoylboucerin 3-O-β-D-digitoxopyranosyl-(1→4)-βD-canaropyranosyl-(1→4)β-D-cymaropyranoside 12,20-di-O-benzoylboucerin 3-O-β-D-cymaropyranosyl-(1→4)-β-D-canaropyranosyl-(1→4)β-D-cymaropyranoside 12,20-di-O-benzoylboucerin3-O-β-D-glucopyranosyl-(1→4)-β-D-digitoxopyranosyl-(1→4)β-D-canaropyranosyl-(1→4)-β-D-cymaropyranoside 12,20-di-O-benzoyl-3β,5α,12β,14β,20-pentahydroxy-(20R)-pregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)-β-D-digitoxopyranosyl-(1→4)-β-D-canaropyranosyl-(1→4)β-D-cymaropyranoside luteolin-4′-O-(α-(L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside)) Ethanol, butanol, chlroform extract 12β-benzoyloxy-8β,14β-dihydroxypregn-20-one-3-O-(3-O-methyl-6-deoxy-β-D-allopyranosyl(1→ 4)-β-D-cymaropyranosyl-(1→ 4)-β-D-cymaropyranoside) 12β-benzoyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-D-glucopyranosyl-(1→4)-3-O-methyl6-deoxy-β-D-allopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→ 4)-β-D-cymaropyranoside) 12β-benzoyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-Dglucopyranosyl-(1→4)-3-O-methyl6-deoxy-β-D-galactopyranosyl-(1→4)-3-O-methyl-6-deoxy-β-D-galactopyranoside) 12β-benzoyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-D-glucopyranosyl-(1→ 6)-β-D-glucopyranosyl-(1→4)-3-O-methyl-6-deoxy-β-D-galactopyranosyl-(1→4)-3-O-methyl6-deoxy-β-D-galactopyranoside) 12β-benzoyloxy-11α-isovaleroyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-D-glucopyranosyl(1→4)-3-Omethyl-6-deoxy-β-D-galactopyranosyl-(1→4)-3-O-methyl-6-deoxy-βD-galactopyranoside) 12β-benzoyloxy-11α-isovaleroyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-D-glucopyranosyl(1→4)-3-O-methyl-6-deoxy-β-D-allopyranosyl-(1→ 4)-β-D-cymaropyranosyl-(1→ 4)-β-D-cymaropyranoside) 12β- benzoyloxy-20-isovaleroyloxy-8β,14β-dihydroxypregnane-3-O-(β-D-glucopyranosyl(1→6)-β-D-glucopyranosyl-(1→4)-β-D-(3-O-methyl-6-deoxy)-galactopyranoside) 12β-benzoyloxy-8β,14β-dihydroxypregn-20-one-3-O-(β-D-oleandropyranosyl-(1→4)-βD-cymaropyranoside) Acylated pregnane glycosides, russeliosides A–D (1–4), in addition to a known flavone glycoside, luteolin 4′-O-β-D-neohesperidoside Russeliosides 14β-benzoyloxy-15β-isovaleroyloxy-16β-hydroxypregn-20-on-3-O-(β-D-3-O-methyl-6deoxyoleandrosopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside) (1) 14β-isovaleroyloxy-15β-benzoyloxy-16β-hydroxypregn-20-on-3-O-(β-D-3-O-methyl-6deoxyoleandrosopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside) (2), 3,4-seco-lup-20(29)-en-3-oic acid methyl ester, Lupeol. β-sitosterol and stigmasterol. luteolin 3′,4′-di-O-β-D-glucopyranoside 12-tigiloyl-tayloron 3β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranoside 12-tigiloyl-tayloron 3β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-βD-cymaropyranoside

Compound Isolated

Anti-inflamatory, Antihyperglycaemic Cytotoxic

Cytotoxic

Reported Activity

Dawidar et al. 2012[33]

Al-Yaha et al. 2000[65] Sattar et al. 2009, 2001[3,9] Mamdouh and Hanaa Raghib 2013[66]

Ramesh et al. 1998[45] Venkatesh et al. 2003[62] Halaweish et al. 2004[63] Halim et al. 1996[64]

Abdullah et al. 2013[61]

References

Medicinal properties of genus Caralluma Muhammad Adnan et al.

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

Whole plant

Whole plant Whole plant

Above-ground parts

Whole plant, above-ground parts

Flowers, stem,fruit

Whole plant

Root Whole plant

C. pauciflora

C. nilagiriana C. fimbriata

C. dalzielii

C. sinaica

C. europaea

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

C. stalagmifera

C. edulis C. longipetala

Pakistan India

India

Italy

Saudi Arabia

Nigeria

India India

India

Methanol extract

Methanol extract

(3β,5α,12β,14β,17α,20S)-12-acetoxy-20-(benzoyloxy)-8,14,17-trihydroxypregnan-3-ylβoleandropyranosyl-(1→4)-β-cymaropyranoside (3β,5α,12β,14β,17α,20S)-12-acetoxy-20-(benzoyloxy)-8,14,17-trihydroxypregnan-3-ylβoleandropyranosyl-(1→4)-β-cymaropyranosyl-(1→4)-β-cymaropyranoside (3β,5α,12β,14β,17α,20S)-12,20-bis-(benzoyloxy)-8,14,17-trihydroxypregnan-3-ylβoleandropyranosyl-(1→4)-β-cymaropyranosyl-(1→4)-β-cymaropyranoside (3β,5α,12β,14β,17α,20S)-12-acetoxy-20-(benzoyloxy)-8,14,17-trihydroxypregnan-3-yl 6-deoxy-3-O-methyl-β-allopyranosyl-(1→4)-β-oleandropyranosyl-(1→4)-β-cymaropyranoside (3β,5α,12β,14β,17α,20S)-12,20-bis(benzoyloxy)-8,14,17-trihydroxypregnan-3-yl 6-deoxy3-O-methyl-β-allopyranosyl-(1→4)-β-oleandropyranosyl-(1→4)-β-cymaropyranosyl(1→4)-β-cymaropyranoside 12β-O-benzoyl-20-O-acetyl boucerin-3-O-6-deoxy-3-Omethyl-β-D-glucopyranosyl-(1→4)β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside, 12b-O-tigloyl-20-O-acetyl boucerin-3-O-β-D-glucopyranosyl-(1→4)-β-D-cymaropyranoside 12β-O-benzoyl-20-O-acetyl boucerin-3-O-β-D-glucopyranosyl-(1→4)-β-D-digitalopyranosyl(1→4)-β-D-cymaropyranosyl-(1→4)-β-Dcymaropyranoside, 12β-O-benzoyl-20-O-acetyl boucerin-3-O-β-D-glucopyranosyl-(1→4)-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl(1→4)-β-D-cymaropyranoside, 12β-O-benzoyl-20-O-tigloyl boucerin-3-O-β-Dglucopyranosyl-(1→4)-β-D-cymaropyranoside 12β-20-O-dibenzoyl boucerin-3-O-β-D-glucopyranosyl-(1→4)-β-D-cymaropyranosyl(1→4)-β-D-cymaropyranoside phenolic alkaloids, glycosides, flavonoids, coumarins, steroids and tannins Monoterpenoids, terpinolene (23.3%), α-terpinene (19.1%) and linalool (18.4%), flavonoids

12β,20-O-dibenzoyl-5α,6-dihydrosarcostin β-oleandropyranosyl-(1→4)-β-cymaropyranosyl(1→4)-β-digitoxypyranosyl-(1→4)-β-cymaropyranosyl-(1→4)-β-cymaropyranoside (1) 12β-O-benzoyl-3β,11α,14β,20R-pentahydroxy-pregn-5-ene(2) 11α-O-benzoyl-3β,12β,14β,20R-pentahydroxy-pregn-5-ene (3) Plant extract Beta sitosterol, palmitic acid,

Antioxidant, anti-inflammatory, antidiabetic, antimicrobial Antidiabetic Antioxidant, anti-inflammatory, antidiabetic, antimicrobial

Semiochemical, antimicrobial

Hypoglycaemic, antidiabetic

Antiproliferative, cytotoxic

Antimicrobial Anti-obesity, appetite-suppressant, genotoxicity

Wadood et al. 1989[73] Vajha et al. 2010[72]

Formisano et al. 2009[70] Meve and Heindick 2005[71] Zito et al. 2010[30] Vajha et al. 2010[72]

Al-Massarani et al. 2012[98] Habibuddin et al. 2008[24]

Prabakaran and Kalimuthu 2013[32] Kamalakkannan et al. 2011[28] Ambadsu et al. 2013[67] Naingade et al. 2013[68] Hadadare and Salankhe 2013[58] Kuriyan et al. 2007[69] Oyama et al. 2007[5] Tanko et al. 2013[31] Leo et al. 2005[4]

Reddy et al. 2011[57]

Muhammad Adnan et al. Medicinal properties of genus Caralluma

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Cultivation Species that belong to subfamily Asclepiadoideae have poor seed germination and viability.[82] Caralluma species are adapted to sunny conditions with good aeration in controlled conditions. Humidity in excess is not needed and thus can be grown outdoors in mild regions with the temperature not less than 10°C; otherwise, they can be grown in a greenhouse or window garden. An ongoing experiment on C. tuberculata has shown some good results so far under the shade in controlled conditions at Kohat, Pakistan. C. tuberculata is also used for ornamental purpose in various areas of Pakistan. Most suitable methods of propagation are through seeds and cuttings, while division is considered as the preferable one. Usually, there are few roots at the bottom of shoots, which can be detached and immediately planted in small pots. The cuttings are inserted in sandy soil to reproduce roots in controlled conditions. Irrigation is only recommended when the soil become dry and would be continued until roots are formed.[83] In case of plants being raised from the seeds, pots are filled with pieces of gravels and sandy compost. Later, the seeds are sowed with a slight cover of soil. The pots are then placed in a controlled environment with 55°C temperature and are covered with a transparent material until sprouting. As the seedlings attain a certain height, they can be transplanted in a pot of sandy soil keeping plant-to-plant distance of 1 inch.[84] The most efficient tissue culturing is regeneration from mature internodal explants to develop an optimal callus in Murashige and Skoog (MS) basal medium by applying various concentration of Auxins, 6-benzyl aminopurine, kinetin (KN) and naphtalene acetic acid. Regenerated plants with well-developed shoots and roots can later be successfully transferred to field/soil.[25] Plant regeneration via organogenesis was initiated for C. arabica by using stem segments excised from young shoots and used as explants for in vitro culture. Stem explants were cultured on MS medium containing different concentrations of KN and indol-acetic acid. In most succulent plants including Caralluma, in vitro propagation has been effectively accomplished for conservation purposes. Additionally, micropropagation protocol of C. edulis and C. adscendens is available, which can be modified for other Caralluma species.[85]

Trade and conservation status The processed form of C. fimbriata as capsules (GENASLIM) is available in the market, which has been claimed effective in reducing body weight.[29] C. adscendens had a market price ranging from US$15 to US$50 per 60 capsules. Certain edible Indian species (C. adscendens, C. fimbriata, C. stalagmifera and C. umbellata) and 8

Pakistani species (C. tuberculata and C. edulis) are available in the respective markets.[21,86] Unfortunately, most species of genus Caralluma are facing considerable pressures in the form of overcollection from wild. As an example, Afghan refugees in the Waziristan region of Pakistan are collecting C. tuberculata unsustainably from the wild and are selling it into the local markets for US$1. Plants are then exported to country’s city markets, where its selling price was observed US$6, which implies a sixfold increase over the local markets. In a study on trade and conservation status of medicinal plants in the northwest region of Pakistan, Hussain et al.[87] have documented C. tuberculata as highly threatened species. The Indian Caralluma species are considered to be threatened due to agricultural extension and population pressure. C. europea is threatened due to the increasing number of holiday villages in Spain.[88] The endemic C. burchardii of the Canary Islands and the two European Caralluma species are protected under the European Commission legislation.[88] Field collection of amateurs should not be underestimated because as a threat, it is secondary to habitat destruction. Tareen et al.[36] worked on the indigenous ethnomedicinal knowledge by the women of Kalat and Khuzdar regions of Pakistan. They concluded over and improper collection, overgrazing, deforestation and urbanization are the major threats to highly valued medicinal plants. This important folkloric medicinal genus is used as an income-generating source by many people in various parts of the world. Moreover, there is also a great demand for Caralluma species from the pharmaceutical industries, herbs and food product dealers, and general public. Hence, to meet these challenges, certain conservation measures are the need of the day.

Ethnobotany For centuries, various plant parts such as roots, bulbs, leaves and flowers have been traditionally used in the treatment of different diseases. The preparation methods, uses and applications of several Caralluma species are well-documented in common ethnobotanical literature.[14,37] Table 1 summarizes 24 species of Caralluma, which are ethnomedicinaly used for various ailments in China, India, Iran, Nepal, Oman, Pakistan, Saudi Arabia, South Africa and Yemen. The traditional use of genus Caralluma ranged from simple ailments (cough/cold and cuts) to very complicated ailments (diabetes, malaria, kidney stones) along other ethnoveterinary uses. Various medicinal uses of Caralluma species have been reported in Arabic and Indian traditional medicine systems as febrifugal, anthelmintic, antirheumatic, antidiabetic, antipyretic, anti-inflammatory, antinociceptive, antioxidant and improve digestions.[5,45] Caralluma extracts have also been found to be appetite-suppressants as well as stimulants of the central nervous system (CNS). Most common

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ethnomedicinal uses of genus Caralluma have been explained as follows.

Antidiabetic The use of traditional remedies against diabetes mellitus has yielded excellent results. Out of 24 reported Caralluma species, seven are being used against diabetes. C. attenuata is a thick succulent perennial herb locally known as ‘Kundaetikommu’ and is eaten raw to cure diabetes in several districts of Andhra Pradesh, India.[19] The same plant is cooked as fresh food and used against diabetes and high blood pressure. Wild and cultivated C. tuberculata in Pakistan is traditionally used in the form of tea to cure diabetes.[15] C. sinaica and C. edulis can cause a significant decrease in glucose level.[73] The extracts of C. attenuata and C. edulis in combination with phlorizin extract can effectively be used to treat diabetes.[32] In Quetta (Pakistan), there is a tradition for the treatment of diabetes to chew fresh plant of C. tuberculata after meal, thrice a day for 1 month.[37]

Medicinal properties of genus Caralluma

C. edulis is cooked as a food with minced meat and is considered to be effective in digestion.[13,91]

Skin infections Skin infections are primarily caused by stings, bites, cuts, burns and contamination of affected exposed parts because of fungi, bacteria and viruses.[92] Different species of Caralluma (C. laciantha, C. stalagmifera, C. arabica and C. tuberculata) are being used for treating skin diseases. Local people are preparing various skin-related ethnomedicinal recipes from these plant species in India, Iran, Nigeria, Oman, Pakistan and Saudi Arabia.[35,37,89] As an example, two stem pieces of C. laciantha are crushed with little lime and cherry, and applied externally on the affected part for 4 days. Similarly, half kilogram of C. laciantha, two handfuls of Mimosa pudica, one spoon of Curcuma langa and little amount of lime juice are mixed together and smeared on the affected parts for 7 days. In another recipe, stem of C. stalagmifera and leaves of Azadirachta indica are crushed together and mixed with oil to apply on the infected part. Moreover, fresh C. tuberculata is chewed for freckles, pimples and blood purification.[36]

Cardiovascular diseases Total three species (C. edulis, C. arabica and C. tuberculata) are used to treat hypertension (Table 1). Common causes of hypertension include obesity, diabetes, high levels of salt intake, insufficient mineral intake, vitamin D deficiency, high level of alcohol consumption, stress, ageing and chronic kidney disorders.[39] Most recipes are orally taken, as an example fresh plant of C. tuberculata is chewed to reduce high blood pressure. Species like C. fimbriata and C. tuberculata are used for blood purification, while C. fimbriata and C. diazielli reduce cholesterol level in the blood.[89] C. tuberculata and C. fimbriata are also traditionally used to purify blood purification in Iran, Pakistan, Saudi Arabia and South Africa.[13,37,89]

Gastrointestinal disorders Most common gastrointestinal problems are constipation, diarrhoea, abdominal pain and ulcer. These diseases may be mild, self-limiting and temporary, or may persist over a longer period of time.[90] Three species including C. edulis, C. tuberculata and C. umbellata are traditionally used for the treatment of such digestive disorders. In Iran and Pakistan, C. edulis is used in promoting appetite, improve digestion and give relief in gastric problems. C. umbellata is burnt in fire and eaten for 5 days regularly on an empty stomach for ulcer and abdominal pain.[18] Whole plant of C. tuberculata is dried and ground to powder, which is taken with water for dysentery, stomach pain, constipation and gastric problems.[38] The stem of C. tuberculata and

Rheumatism There are more than 100 rheumatic diseases caused due to inflammation, swelling and pain in joints or muscles.[93] According to folkloric practitioners in Africa, Caralluma species are useful in treating rheumatism.[65] In total, three species of Caralluma including C. tuberculata, C. edulis and C. adesecnse are traditionally used as antirheumatism.[20,21] Caralluma extracts can cause increased secretion of the synovial fluids, which can enhance the joint efficiency and mobility. Traditional recipes of Caralluma species are taken as a tonic to give strength to joints for bearing greater loads.[36,89] Moreover, C. edulis is cooked as food and considered nutritive with good efficacy against rheumatism.[14]

Antipyretics Historically, several plant species are traditionally used as antimalarial and antipyretics. C. tuberculata and C. edulis are more effective against fever. The stem of C. tuberculata is very effective as antipyretic,[91] while its above-ground part has been proved scientifically for its antimalarial activity.[20] The succulent stem of C. edulis is cooked as food and considered very effective treatment in reducing fever.[13,15]

Other uses In the rural India, C. fimbriata is cooked and eaten with spices as a food. Moreover, it is also preserved as chutneys and pickles. It is eaten in raw by labourers as an appetite and thirst suppressant, and endurance enhancer. Fresh juice

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of the C. attenuate along with black pepper is recommended in the treatment of migraine.[45] The above-ground part of C. oxyacantha is taken along with honey to reduce kidney pain in Iran.[13] C. laciantha and C. bhupenderiana in India have large number of ethnoveterinary uses.[21] C. negevensis is used as anticancer agent in Spain.[8] Powdered C. tuberculata is taken along water to treat jaundice in Pakistan.[36]

Chemistry The medicinal properties of Caralluma have been attributed to the glycosides contained therein (Table 2). A glycoside is a condensed product obtained from a sugar and non-sugar compound and may have further components such as ring structures that are substituted or non-substituted. The key and characteristic phytochemical constituents in Caralluma

CH3 CH3

CH3

H

H

OH

HO H Figure 2

Basic skeleton of pregnane.

are pregnane glycosides, flavone glycosides, megastigmane glycosides, bitter principles, triterpenes and saponins.[7,8]

Pregnanes and their glycosides Pregnanes are C-21 steroidal compounds (Figure 2) having perhydro-1,2-cyclopentanophenanthrene ring system with β-oriented angular methyl groups at C-10 and C-13, and a two carbon side-chain at C-17.[94] Usually, pregnane derivatives possess a β-configuration at C-14 and bear a hydroxy functionality at this position. The configuration of pregnane derivatives at C-5 is usually α and C-3 hydroxyl group is always β-oriented.[94,95] In common, the Caralluma plants contain high level of pregnanes, their glycosides or esters, which may be useful in the treatment of rheumatism, diabetes and leprosy, and can act as antiseptics as well as disinfectants.[9] Various phytochemical studies on genus Caralluma have reported the isolation of pregnane glycosides or their esters[20] (Figure 3). As an example, C. adscendens var. gracilis and C. pauciflora have resulted the isolation of a pregnane glycoside (12β,20-O-dibenzoyl-5α,6-dihydrosarcostin -β-oleandropyranosyl-(1→4)-β-cymaropyranosyl-(1→4)β-digitoxypyranosyl-(1→4)-β-cymaropyranosyl-(1→4)-βcymaropyranoside) and two pregnanes (12β-O-benzoyl -3β,11α,14β,20R-pentahydroxy-pregn-5-ene and 11α-Obenzoyl-3β,12β,14β,20R-pentahydroxy-pregn-5-ene).[96] Some of the pregnane glycosides including Penicilloside E have showed very potent antitrypanosomal activity.[97] The acylated pregnane glycosides have also been reported.[98] The isolation studies on the non-polar fractions of

O

O O

O H3C CH3

H3C CH3

O

OH CH3

RO H H3C

H3C

HO MeO

O

O

HO MeO

OMe

OMe

H3C

H3C

R= H3C

O

O

OH

O

O

H3C HO MeO

Figure 3

10

O

OMe

OMe H3C

O

R=

O

H3C HO MeO

OMe OH

O

O

O

O

OH

H3C R=

OH

OH

RO

O

O

O

OH

OH

R= H3C

H

CH3

OH

CH3

H3C

O

O OMe

OH

Some important pregnane glycosides of Caralluma species. © 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

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Medicinal properties of genus Caralluma

C. umbellata roots by using non-polar solvents like n-hexane, benzene and acetone have resulted non-polar pregnanes 3b-hydroxy-pregn-5-ene and 3b,14 b-dihydroxy pregn-5-ene.[17] Pregnane, with lactone functionality (3-Oβ-D-glucopyronosyl, 8β-isopropoxy, 14β-ethynyl,pregn5en-21, 21-dimethy16,17lactone) has been isolated from genus Caralluma.[46] Along with esters, pregnane glycoside diesters from genus Caralluma have also been reported.[66] The above-ground parts of C. russeliana yielded four pregnane glycosides, russeliosides A–D.[97] Glycosidation in pregnane glycosides occurs at C-3 or C-20 most frequently.[99] The sugar moiety is usually linked to an alcoholic hydroxyl group of the pregnane aglycone[97,100,101] and is generally composed of a linear rather than a branched saccharide chain.[102] In some cases, the sugar was also found to be linked at C-14 of the aglycone, which is a rare site of substitution.[99]

The flavone glycoside luteolin-3′-O-α-L-rhamnopyranoside and the flavonol glycoside kaempferol-3-O-β-Dglucopyranoside-4′-O-α-L-rhamnopyranoside have been separated and identified from C. arabica through centrifugal counter-current chromatography.[106] From the n-BuOH fraction of C. negevensis methanol extract, two flavone glycosides, luteolin-3′-O-β-D-glucopyranoside4′-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside and luteolin-3′,4′-di-O-β-D-glucopyranoside have been reported.[7]

Triterpenoids There is presence of triterpenoids in Carraluma species. The triterpenes squalene, β-sitosterol acetate, lupeol, lupeol acetate, guimarenol, lupenone and a triterpene, 3,4-secolup-20(29)-en-3-oic acid methyl ester were isolated from C. buchardii.[107]

Other steroids and their glycosides

Other compounds

C-21 steroidal glycosides have been reported from the whole plant of Caraluma umbellate.[103] Five new pregnane glycosides, caradalzielosides A–E (1–5) were isolated from the above-ground parts of C. dalzielii.[104] Acylated steroidal glycosides from C. tuberculata have also been reported.[105]

C. tuberculata showed the presence of cardiac glycosides, caumarine, emodins, anthocyanin, betacyanin, alkaloids, tannins, saponins and some reducing sugars.[108] Moreover, GC analysis of C. europaea indicated the presence of some volatile compounds including essential oils, hydrocarbons and some other fatty acids.[30,70]

Megastigmane glycosides The megastimane compounds have α-ionol basic skeleton (Figure 4). The isolation of some megastigmane with hydroxyl functionality at C-2 has been reported from the n-BuOH fraction of the methanol extract of C. negevensis.[7] Flavonoid aglycones and glycosides occur in limited diversity and quantity in Apocynaceae compared with many other angiosperm families.[95] Luteolin-4′-O(β-(L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside) or luteolin-4′-O-neohesperidoside was isolated from several Caralluma species. Kaempferol-7-O-α-L-rhamnopyranosyl(1→2)-β-D-glucopyranoside and kaempferol-3-O-α-L rahmnopyranoside-(1→6)-β-D-glycopyranoside were isolated from the fresh vegetative part of C. tuberculata.[49]

Pharmacological reports Plants are an important source for the development of new chemotherapeutic agents. Medicinal plants contain bioactive substances such as alkaloids, terpenopids, flavonoids, steroids, tannins and some phenolic compounds, which have definite physiological actions on the human body.[109] Approximately 130 drugs, all single chemical entities have been extracted from higher plants.[110] Many Caralluma species are traditionally used to cure various diseases but not all tested for their biological activity. A number of in vitro and to a lesser extent in vivo biological studies have been performed on crude extracts

OH

OH CH3

CH3

O

O CH3

CH3 CH3

CH3 OGlc Figure 4

(1

CH3

6)

rha

CH3 OGlc

(1

6)

rha

Some important megastigmane glycosides of Caralluma plants.[7]

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No. of species

8 6 4 2

A

or y io xi da H yp nt ol ip id im ic A nt ic an ce A r nt io be sit y nt

A

m

at

xi ci ty la m

nt

i-i nf

Cy to

to

ob ic r

im

nt A

A

nt

id ia b

et

ic

ia l

0

Figure 5

Pharmacological activities

Number of pharmacological activity of Caralluma species.

and several pure constituents of Caralluma species. Mostly, antidiabetic and antimicrobial activity of Caralluma species have been reported (Figure 5). C. umbellata, C. adscendens, C. attenuate, C. sinaica, C. stalagmifera, C. edulis and C. longipetala are pharmacologicaly active against diabetes, while C. tuberculata, C. nilagiriana, C. europaea and C. Longipetala have shown antimicrobial potential. Very few species have been checked for their antilipidaemic, anticancer and anti-obesity potential. Only two species (C. umbellata and C. adscendens) have been reported for their antilipidaemic and anticancer activity. Moreover, C. fambriata have shown anti-obesity activity. Species like C. umbellata, C. tuberculata, C. adscendens, C. stalagmifera and C. longipetala have extensively explored for variety of pharmacological activity as compared with other species (Table 2). These studies have helped in identifying active principles responsible for such activity and developing drugs for therapeutic uses in human beings. Contrary to the synthetic drugs, plant-derived compounds are less associated with side effects and have an enormous therapeutic potential to heal many infectious diseases.

Antimicrobial activity Microorganisms can cause various diseases in human beings from mild to acute and chronic. In this study, different solvent extracts of Caralluma species have been reviewed against a range of microorganisms affecting both humans and animals. For instance, the methanolic, aqueous and chloroform extracts of C. nilagiriana were studied against several bacterial strains.[32] Methanolic extract has showed high activity against Pseudomonas aeruginosa (30 ± 1.84 mm inhibition zone) and Salmonella typhi (15 ± 1.56 mm inhibition zone) in comparison with aqueous extract. In another study, fatty acids in C. europaea have shown antimicrobial activity.[30] Moreover, ethanolic 12

and aqueous extracts of C. adscendens have shown prominent activity against P. aeruginosa and Escherichia coli.[56] The activity was comparable with that of chloramphenicol as a standard. Similarly, ethanolic extracts of C. tuberculata and C. edulis were active against both Gram-positive bacteria (Staphylococcus aureus, Streptococcus viridens) and Gram-negative bacteria (E. coli, Salmonella typhi and Shigella sonnei). C. edulis showed more inhibitory effects than C. tuberculata.[86] Ethanolic and methanolic extracts of Caralluma may contain certain flavonoids that are responsible for various antibacterial activity. Most fungus infections are attributed to Aspergillus fumigatus, followed by A. flavius and A. terreus,[111] which may result in significant morbidity and mortality. A. niger is less commonly reported as a cause of invasive disease; however, it is associated with cutaneous infections and pulmonary disease.[112] Khan et al.[54] found that the methanolic extract of C. tuberculata has significantly inhibited A. flavius more than A. niger. In another test, ethylacetate and butanol extracts of C. tuberculata showed significant antifungal in vitro activity against A. niger, Candida albicans and Pheretima posthuma.[113] The plant is highly toxic because of the oxypregnane glycosides penicillosides A–G. Penicilloside E showed high antitrypanosomal activity in vitro. Higher plants have the potential for new phytochemicals, which can be used against some highly resistant microorganisms.[113]

Antioxidant activity Oxidative damage due to free radicals may be related to certain diseases such as atherosclerosis, diabetes, cancer, inflammation and cirrhosis.[11] These days, antioxidants are gaining more importance as health promoters in the treatment of cardiovascular problems, atherosclerosis, cancer and the ageing process. Many plant-based antioxidant compounds have been identified as free-radical scavengers. Caralluma extracts were found to have different levels of antioxidant properties in different test models used. Four Caralluma species have showed potential free-radical scavenging activity expressed as inhibitory concentration (IC50), 27, 36, 32, 37(μg/ml), respectively.[114] C. longipetala has greater antioxidant property than C. stalagmifera and C. adscendens. These results suggested that the antioxidant capacity of methanolic extracts of four Caralluma species is due to the presence of phenolic compounds to a great extent. Anti-inflammatory activity of the methanolic extracts of C. lasiantha, C. adscendens, C. stalagmifera and C. longipetala was studied by 5-Lox activity. C. adscendens, C. stalagmifera and C. longipetala have shown IC50 values 24, 11.8 and 12.5 μg/ml, respectively.[72] Methanol and water extracts were found to have good total phenolic and flavonoid contents with potent antioxidant and free-radical scavenging activity. The antioxidant activity was correlated

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well with the amount of total phenolics present in the extracts.[59] Methanolic extract and chloroform fraction of C. tuberculata was also tested for antioxidant activity by Rauf et al.[11] β-Sitosterol isolated from C. adcendenscan can be used as an antioxidant.[58] Because of the strong antioxidant activity in the extracts derived from above-ground parts of C. edulis, Caralluma species are gaining more interest from nutraceutical companies.[49]

Medicinal properties of genus Caralluma

HO O

HO

O

HO OR1

R2O

CH3

O HO HO OH

O H3C

OH O

H3CO

O

O

OH

Anti-obesity The known pharmaceutical options for the treatment of obesity are thermogenesis, lipase inhibitors and compounds that suppress appetite or stimulate the CNS.[115] All the three approaches to the obesity treatment and management have been found to with unacceptable side effects. An interesting fact first observed is that the maximum caratuberside-bouceroside synergy is found when the caratuberside-bouceroside ratio is substantially equal to the caratuberside-bouceroside ratio (CBR) found in C. indica. Three other species, namely, C. fimbriata, C. attenuata and C. tuberculata substantially have the same ratio value and same glycoside content as C. indica. These four species are referred to hereinafter as Group I Caralluma species. Four more species, namely, C. stalagmifera, C. umbellata, C. lasiantha and C. edulis also have substantially the same CBR but somewhat lesser total content of glycosides than the Group I species. The latter four species are referred to hereinafter as Group II species, and the caratuberside-bouceroside (pregnane group of glycosides) ratio is referred to as the CBR. Treatment with C. fimbriata extract at a dose of 100 mg/kg/day has significantly reduced (P < 0.05) the increase in body weight and lipid profile levels as compared with the CD (cafeteria diet) control group. Hence, C. fimbriata might be useful in the treatment of obesity[67] as it is capable of decreasing appetite and prevent deposition of fats. C. fimbriata blocks the formation of two enzymes (acetyl co-enzyme A and malonyl co-enzyme A), which are the building blocks of fat synthesis.[68] The appetite suppressing properties of C. fimbriata have been attributed to the active component pregnane glycosides. It has been hypothesized that C. fimbriata may down-regulate ghrelin synthesis in the stomach and neuropeptide-Y in the hypothalamus, resulting in appetite suppression leading to reduce obesity.[67] Developing evidence suggests that taking a Caralluma extract for 60 days might decrease waistline, hunger and calorie intake.[116] In one of the human clinical trials conducted in 2007, researchers compared baseline indicators of obesity like serum lipids, blood sugar, anthropometric measurements, calorie intake and appetite suppression with those after 60 days of consumption of C. fimbriata extract.[69] The results showed decrease in body weight, body mass index, body fat,

CH3

CH3

Carumbelloside III; R1 = R2 = H Carumbelloside 1V; R1 = Bz, R2 = H Carumbelloside V; R1 = R2 = Bz Figure 6

Bz =

Cytotoxic steroids (Carumbelloside III-V) of Caralluma.

hip circumference and food intake. The authors of this study concluded that Caralluma extract does seem to possess weight-reducing abilities. Similar results have also been reported by Lawrence and Choudhary.[29] In an animal study conducted more recently, the authors proved not only the anti-obesogenic but also anti-atherosclerotic abilities of C. fimbriata.[31] These studies can help in the development of natural anti-obesity drugs.

Anticancer The ethyl acetate fraction of C. tuberculata was found to be the most potent antiproliferative fraction against breast cancer (Michigan Cancer Foundation-7 (MCF7) human breast oestrogen-dependent adenocarcinoma and MDAMB-468 human breast oestrogen-independent adenocarcinoma) and other tumour cell lines (Caco-2 human colon adenocarcinoma). Steroid glycosides isolated from C. tuberculata were found to possess moderate, micromolar cytotoxic activity on breast cancer and other cells in vitro.[10] Certain cytotoxic steroids have already been identified in genus Caralluma (Figure 6). Β-sitosterol isolated from C. adcendens is proved to be chemopreventive in the colon cancer and breast cancer cell line by inhibiting the cancer cell proliferation. However, in the in vitro toxicological studies, chronic administration of β-sitosterol was found to be safe and non-toxic.[58] Hence, Carraluma species screened for phytochemical constituent seemed to have the potential to act as a source of useful drugs and also to improve the health status.

Hyperglycaemic activity The rapidly increasing diabetes mellitus is becoming a serious threat to human health around the globe. Different species of genus Caralluma have been proven very effective against diabetes. The extract of C. diazielli has significantly reduced (P < 0.05) levels of all serum liver enzymes (alanine

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transaminase, aspartate aminotransferase, alkaline phosphatase) on fructose-induced diabetes in Wistar rats.[31] Human liver microsome studies showed that β-sitosterol isolated from C. adcendens inhibits the cholesterol absorption and can be used as antidiabetic.[58] Ethanolic and aqueous extracts of C. tuberculata were diluted with distilled water and showed hypoglycaemic activity at a dose of 70.42 mg/kg in allaxon-fed diabetic male Albino rats. The blood glucose level was reduced from 278.61 mg/100 ml to 248.37 mg/100 ml in ethanolic extract-treated diabetic rats, while in aqueous-treated diabetic rat, blood sugar level was lowered from 317.63 mg/100 ml to 295.64 mg/100 ml after 30–60 min of extract administration.[86]

Hypolipidaemic activity Cholesterol reducing action of the aqueous extract of C. adcendens indicated hypolipidaemic activity.[60] Treatment with aqueous extract of C. fimbriata at three different doses can significantly decrease the level of total cholesterol and LDL cholesterol as compared with controls. Aqueous extract at different doses (250, 500, 750 mg/kg/p.o.) have significantly lowered. Methimazole induced elevated level of total cholesterol (P < 0.01) and triglyceride (P < 0.05). Moreover, C. umbellata has also shown antilipidaemic activity, which might be due to the presence of active constituents (Table 2).

Other pharmacological activity Various other potential activity have also been reported from different Caralluma species. For instance, Zito et al.[30] have reported that aromatic compounds found in stems and fruits of C. europaea are semiochemicals for many insects. C. umbellata has been proven with anti-eczemic activity, while C. tuberculata has shown antitrypanosomal activity.

Toxicity In total, six Caralluma species have reported toxic activity. C. tuberculata has phytotoxic potential. Methanolic extract of C. tuberculata (1000 μg/mL) inhibits the growth of shoot and roots (hypocotyls & radicals) of the rice seeds (Oryza sativa).[54] In another experiment, ethanolic, ethylacetate and aqueous extracts of C. tuberculata were also tested for their toxicity on Artemia salina. Ethanol and ethylacetate show significant toxicity, while aqueous extract was found to be non-toxic.[86] C. dalzielii, C. retrospiciens, C. quadrangula, C. negevensis and C. tuberculata have shown cytotoxic activity in vitro. C. fambriata has shown genotoxicity activity, and hence, its supplements are not recommended for pregnant or lactating women. Animal studies and human clinical trials conducted on C. fimbriata have reported no adverse 14

effects.[28,117] In an animal-conducted trail on Wistar rats, acute toxicity of the ethanolic extract of C. dalzielli was found at 2.154 mg/kg orally.[31] Pregnane glycoside extracted from C. quadrangular showed significant cytotoxic activitiy against breast cancer (MCF7) cell line.[61] Caralluma seems to be safe for most people when 500 mg of the extract is taken twice a day for up to 60 days; however, the long-term safety is not known. Caralluma might cause some mild side effects such as stomach upset, gastric problem and constipation. These side effects usually go away after a week of use. The appropriate dose of Caralluma depends on several factors such as the user’s age, health and several other conditions. At this time, there is not enough scientific information to determine an appropriate range of doses for Caralluma.

Conclusions This review emphasizes that the ethnobotanical, phytochemical, pharmacological, conservation and cultivation values of genus Caralluma species are an indication of its high importance globally. The available scientific research on Caralluma signifies its importance as medicinal plant used in a wide range of ethnomedicinal treatments, especially for diabetes, obesity, gastrointestinal problems, blood disorders, skin problems and cancer. The medicinal properties of Caralluma are attributed to the presence of variety of chemicals like pregnane glycosides, flavonoids, steroids and their glycosides and triterpinoids, respectively. The increasing medicinal importance of Caralluma is demanding the investigation of unexplored species of this genus for the possible discovery of more potential phytochemicals. Such studies can lead to the improvement in drug system by discovering new constituents for the welfare of human beings. Very few species of this genus such as C. tuberculata, C. attenuate and C. fimbriata have been subjected to stringent scientific evaluation. Most of the studies in this review have established a scientific basis to the use of Caralluma species in traditional medicine. As an example, pharmacological studies confirmed the antimicrobial, anti-obesity, anticancer, hyperglycaemic and hypolipidaemic activity of these plants. However, no sufficient information is available on the toxicity of genus Caralluma or its derived medicines that needs some extensive research. Moreover, no antiviral activity of this genus has been reported from the literature. Hence, Caralluma species may be tested against different viral strains along untested bacterial and fungal strains to explore further its medicinal potential. Clinical trials of C. fimbriata have shown good results against diabetes and obesity. Similarly, β-sitosterol isolated from C. adcendens has shown good potential as chemopreventive in the colon

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and breast cancer cell lines. However, fewer studies have been carried out particularly on anticancer activity of Caralluma. Many Caralluma species such as C. longipetala and C. tuberculata have been tested for their antioxidant properties and have shown encouraging results. The diverse uses of genus Caralluma have made it susceptible to overexploitation, and it may become threatened due to its high trade. Caralluma is not an invasive species so modern cultivation techniques should be developed for its commercial exploitation. Furthermore, tissue culture techniques must be developed to enhance production and preserve natural germplasms of Caralluma species. For sustainable and long-term conservation of Caralluma species, there is a need to actively involve the acquiescence of local

References 1. Stewart RA. An annotated catalogue of the vascular plants of West Pakistan and Kashmir. In: Nasir E, Ali SI, eds. Flora of West Pakistan. Pakistan: University of Karachi, 1972: 1–1028. 2. Naik RM, Krishnamurthy YL. Xerophyte Caralluma stalagmifera var. longipetala (Asclepiadaceae): a new record to the flora of Karnataka, India. J Threat Taxa 2012 4: 2656– 2659. 3. Sattar EA et al. Antiplasmodial and antitrypanosomal activity of plants from the Kingdom of Saudi Arabia. J Nat Med 2009; 63: 232–239. 4. Leo MD et al. New pregnane glycosides from Caralluma dalzielii. Steroids 2005; 70: 573–585. 5. Oyama M et al. Five new steroidal glycosides from Caralluma dalzielii. Helv Chim Acta 2007; 90: 63–71. 6. Aruna V et al. Micropropagation of three varieties of Caralluma adscendens via nodal explants. J Plant Biochem Biotechnol 2009; 18: 121– 123. 7. Bader A et al. Further constituents from Caralluma negevensis. Phytochemistry 2003; 62: 1277–1281. 8. Braca A et al. New pregnane glycosides from Caralluma negevensis. Tetrahedron 2002; 58: 5837– 5848. 9. Sattar EA et al. Acylated pregnane glycosides from Caralluma russe-

10.

11.

12.

13.

14.

15.

16.

17.

people in planning, implementation, monitoring and evaluation processes. Moreover, local collectors of Caralluma must be trained for its collection, drying and processing techniques to reduce overexploitation. Furthermore, comprehensive policy is required regarding the trade and conservation of Caralluma to control severe genetic erosion of useful genotypes from the population.

Declaration Acknowledgements The authors are highly indebted to departmental colleagues for their support.

liana. Phytochemistry 2001; 68: 1459– 1463. Waheed A et al. Novel acylated steroidal glycosides from Caralluma tuberculata induce caspasedependent apoptosis in cancer cells. J Ethnopharmacol 2011; 137: 1189– 1196. Rauf A et al. Phytochemical, phytotoxic and antioxidant profile of Caralluma tuberculata N. E. Brown. Wudpecker J Pharm Pharmacol 2013; 2: 21–25. Ali SI, Qaiser M Flora of Pakistan. no. 1–215 (1972–2010), Pakistan.http:// www.efloras.org/flora_page.aspx? flora_id=5, accessed on 9 November 2010. 2010. Safa O et al. An ethnobotanical survey on Hormozgan Province, Iran. Avicenna J Phytomed 2013; 3: 64–81. Mahmood A et al. Ethnomedical survey of plants from District Sialkot, Pakistan. J Appl Pharm 2011; 2: 212–220. Ali H et al. Ethnobotanical profile of some plant resources in Malam Jabba valley of Swat, Pakistan. J Med Plants Res 2011; 5: 4676–4687. Ahmad M et al. Traditional herbal remedies used for the treatment of diabetes from District Attoc (Pakistan). Pak J Bot 2009; 41: 2777–2782. Kishore M et al. Chemical examination of medicinal plant ‘Caralluma unbellata’Asclepiadaceae) roots. Int J

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

18.

19.

20.

21.

22.

23.

24.

Appl Biol Pharm Technol 2010; 1: 545–549. Karuppusamy S. Medicinal plants used by Palyan tribe of Sirumalai Hills of Southern India. Nat Prod Radiance 2007; 6: 436–442. Kumar AS et al. A review on medicinal plants with potential anti diabetic activity. Int J Phytopharmacol 2011; 2: 53–60. Sattar EA et al. Acylated pregnane glycosides from Caralluma tubreculata and their anti parasitic activity. Phytochemistry 2008; 69: 2180–2186. Naik RM et al. Nutritive value and mineral composition of edible Caralluma and Boucerosia species from the arid areas of Karnataka. Int J Agric Environ Biotechnol 2012; 5: 117–125. Gowri S, Chinnaswamy P. Evaluation of invitro antimutagenic activity of Caralluma adscendens Roxb. in bacterial reverse mutation assay. J Nat Prod Plant Resour 2011; 1: 27–34. Nawal M et al. Study of the in vitro antiplasmodial, antileishmanial and antitrypanosomal activities of medicinal plants from Saudi Arabia. Molecules 2012; 17: 11379–11390. Habibuddin M et al. Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits. J Ethnopharmacol 2008; 117: 215–220.

15

Medicinal properties of genus Caralluma

25. Karthik PM et al. In vitro propagation of a rare succulent medicinal plant Caralluma diffusa (Wight) N.E.Br. Res Plant Biol 2003; 3: 8–17. 26. Ramadevi T et al. In vitro shoot multiplication from nodal explants of Boucerosia diffusa weight – an endemic medicinal plant. Indian J Biotechnol 2012; 11: 344–347. 27. Ugraiah A et al. In vitro shoot multiplication and conservation of Caralluma bhupenderiana Sarkaria-An endangered medicinal plant from South India. Afr J Biotechnol 2011; 10: 9328–9336. 28. Kamalakkannan S et al. Antiobesogenic and antiatherosclerotic properties of Caralluma fimbriata extract. J Nutr Metab 2010; 2010: 1–6. 29. Lawrence RM, Choudary S. Caralluma fimbriata in the treatment of obesity. 12th Annual World Congress of Anti-Aging Medicine. 2004 30. Zito P et al. Essential oil composition of stems and fruits of Caralluma europaea N.E.Br. (Apocynaceae). Molecules 2010; 15: 627–638. 31. Tanko Y et al. Effect of ethanolic extract of Caralluma diazielli on serum lipid profiles on fructose induced diabetes in wistar rats. Scholar Res 2013; 4: 162–166. 32. Prabakaran R, Kalimuthu K. Antibacterial activity of the whole plant of Caralluma nilagiriana Kumari et Subba Rao – an endemic medicinal plant species. Int J Pharm Bio Sci 2013; 4: 42–48. 33. Dawidar AM et al. Phytochemical investigation of Caralluma wissmannii. Res J Pharm Biol Chem Sci 2012; 3: 882–892. 34. Zakaria MNM et al. Anti-nociceptive and anti-inflammatory properties of Carallumaarabica. J Ethnopharmacol 2001; 76: 155–158. 35. Shah A et al. Sacredjungle: a traditional way of conserving endangered ecosystem and biodiversity in semi tribal are, Kurd sharif & SHO (District Karak, Khyber Pakhtunkhwa), Pakistan. Sci Technol Dev 2012; 31: 312–326. 36. Tareen RB et al. Indigenous knowledge of folk medicine by the women 16

Muhammad Adnan et al.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

48.

49.

of Kalat and Khuzdar regions of Balochistan, Pakistan. Pak J Bot 2010; 42: 1465–1485. Manzoor M et al. Uses of fruits, vegetables and herbs for the treatment of diabetes by the people of Quetta city. Sci Technol Dev 2013; 32: 24–27. Marwat SK et al. Tracing the useful ethno phytomedicinal recipes of angiosperms used against jaundice and hepatitis in Indo-Pak subcontinent. World Appl Sci J 2012; 18: 1243–1252. Mahmood T et al. Molecular and morphological characterization of Caralluma species. Pak J Bot 2010; 42: 1163–1171. Zabihullah Q et al. Ethnobotanical survey in Kot Manzaray Baba Valley Malakand Agency, Pakistan. Pak J Plant Sci 2006; 12: 115–121. Ray S et al. Anti-inflammatory activity of Carumbelloside-III, isolated from Caralluma umbellata. J Pharm Healthcare Manage 2011; 2: 83–88. Kunert O et al. Steroidal glycosides from Caralluma umbellata. Phytochemistry 2009; 2: 134–138. Jeya K et al. Study of phytochemical constituents in Caralluma Umbellata by GC-MS analysis. Int J Pharm Sci Invent 2013; 2: 37–41. Lin LJ et al. Pregnane glycosides from Caralluma umbellata. Phytochemistry 1994; 35: 1549–1553. Ramesh M et al. Antinociceptive and anti-inflammatory activity of a flavonoid isolated from Caralluma attenuata. J Ethnopharmacol 1998; 62: 63–66. Kalyani K et al. A novel pregnane glycoside from the Caralluma Umbellata haw (Asclepiadaceae) roots. J Nat Sci Res 2013; 3: 55–61. Qiu SX et al. Bisdesmosidic pregnane glycosides from Caralluma lasiantha. Phytochemistry 1999; 50: 485–491. Ahmad MM et al. Anti-inflamatory activity of Caralluma tubreculata alcoholic extract. Fitoterapia 1993; 46: 357–360. Rizwani GH et al. Flavone glycosides of Caralluma tuberculata N. E. Brown. Pak J Pharm Sci 1990; 3: 27–32.

50. Khattak KF. Nutrient composition, phenolic content and free radical scavenging activity of some uncommon vegetables of Pakistan. Pak J Pharm Sci 2011; 24: 277–283. 51. Al-Bekairi AM et al. Effectof Caralluma tuberculata on the cytological and biochemical changes induced by cyclophosphamide in mice. Food Chem Toxicol 1992; 30: 719–722. 52. AL-Harbi MM et al. Evaluation of Caralluma tubreculata pretreatment for the protection of rat gastric mucosa against toxic damage. Toxicol Appl Pharmacol 1994; 128: 1–8. 53. Ahmad VU et al. New pregnane glycosides from Caralluma tuberculata. J Nat Prod 1988; 51: 1092– 1097. 54. Khan MZ et al. Biological screening of methanolic crude extracts of Caralluma tuberculata. Int J Indigenous Med Plants 2013; 46: 2051– 4263. 55. Tatiya AU et al. Anti-toxident and hypolipidemic effect of Caralluma adscendens Roxb. in alloxanized diabetic rats. Int J Pharmacol 2010; 6: 400–406. 56. Kulkarni A. Evaluation of antibacterial activity of caralluma adscendens Roxb. Stem. Int Res J Pharm 2012; 3: 269–270. 57. Reddy KM et al. Minor pregnanes from Caralluma adscendens var. Gracilis and Caralluma pauciflora. Fitoterapia 2011; 82: 1039–1043. 58. Hadadare M, Salunkhe V. Simultaneous estimation of beta sitosterol and palmitic acid from methanolic extract of Caralluma Adscedens var Fimbriata by UV spetrophotometry. Res J Pharm Biol Chem Sci 2013; 4: 225–232. 59. Maheshu V et al. Antioxidant capacity and amino acid analysis of Caralluma adscendens (Roxb.) Haw var. fimbriata (wall.) Grav & Mayur.aerial parts. Int J Food Sci Technol 2012. doi: 10.1007/s13197012-0761-5. 60. Sakore S et al. Hypolipidemic activity of Caralluma adscendens on triton and methimazole induced

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

Muhammad Adnan et al.

61.

62.

63.

64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

hyperlipidemic rats. Pharmtechmedica 2012; 1: 49–52. Abdullah HM et al. Acylated pregnane glycosides from Caralluma quadrangula. Phytochemistry 2013; 88: 54–60. Venkatesh S et al. Antihyperglycemic activities of Caralluma attenuate. Fitoterapia 2003; 74: 274–279. Halaweish FT et al. Polyoxypregnane glycosides from Caralluma retrospiciens. Phytochem Anal 2004; 15: 189– 194. Halim AF, Khalil AT. Pregnane glycosides from Caralluma retrospiciens. Phytochemistry 1996; 42: 1135–1139. Al-Yaha MAA et al. Pregnane glycosides from Caralluma russeliana. J Nat Prod 2000; 63: 1451–1453. Mamdouh AM, Hanaa MR. Two new pregnane glycoside diesters from Caralluma russeliana. Nat Prod Res 2013; 27: 1287–1292. Ambadsu B et al. Effect of Caralluma fimbriata extract on appetite and lipid profile in rats fed with hypercalorie/.cafeteria diet. Int J Pharm Bio Sci 2013; 4: 788–794. Naingade SS et al. Caralluma fimbriata: an overview. Int J Pharm Bio Sci 2013; 3: 281–286. Kuriyan R et al. Effect of Caralluma fimbriata extract on appetite, food intake and anthropometry in adult Indian men and women. Appetite 2007; 48: 338–344. Formisano C et al. Headspace volatile composition of the flowers of Caralluma europaea N.E.Br. (Apocynaceae). Molecules 2009; 14: 4597–4613. Meve U, Heneidak S. A morphological, karyological and chemical study of the Apteranthes (Caralluma) europaea complex. Bot J Linn Soc 2005; 149: 419–432. Vajha M et al. Evaluation of immunostimulating activities of Caralluma species. Int J Pharmacognosy Phytochem Res 2010; 2: 1–4. Wadood A et al. Effect of Acacia Arabica and Caralluma edulis on blood glucose levels of normal and

Medicinal properties of genus Caralluma

74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

allox andiabetic rabbits. J Pak Med Assoc 1989; 9: 208–212. Gilbert MG. A review of Caralluma R. Br. and its segregates. Bradleya 1990; 8: 1–32. Meve U, Liede S. Subtribal division of Ceropegieae (ApocynaceaeAsclepiadoideae). Taxon 2004; 53: 61–72. Jagtap AP, Singh P. Fascicles of Flora of India, Fascicle 24. Calcutta: Botanical Survey of India, 1999: 190– 211. Ali SI. Flora of West Pakistan. In: Nasir E, Ali SI, eds. Asclepiadaceae, Vol. 150. Karachi, Pakistan: Depatment of Botany, Universty of Karachi, 1983: 1–62. Ansari NM et al. Antioxidant activity of five vegetables traditionally consumed by South-Asian migrants in Bradford, Yorkshire, UK. Phytother Res 2005; 19: 907–911. Bensuzan K. Taxonomy and conservation status of Moroccan stapeliads (Apocynaceae-AsclepiadoideaeCeropegieae-Stapeliinae). Bull Inst Sci Univ Rabat 2009; 31: 67–77. Evans WC. Trease and Evans, Pharmacognosy, 15th edn. London, Toronto, Sydney: W.B Saunders Company, 2002. Saxena AK, Sarbhai RP. A Text Book of Botany. High Court Road, Kitab Ghar: Oxford Press, 1975. Samydurai P, Thangapandian V. The effects of different treatments on promotion of seed germination, successive of seedling growth of Decalepis hamiltonii Wight & Arn. A globally endangered medicinal plant. J Res Conserv Biol 2012; 1: 36–40. Mustafa K A report on ‘Domestication of wild Caralluma tuberculata’ Department of Botany, Kohat Univeristy of Science and Technology, Kohat, Pakistan, 2014. Albers F, Meve U. Asclepiadaceae. Illustrated Handbook of Succulent Plants, Vol. 191. Heidelberg: Springer-Verlag, 2002: 46–63. Bouhouche N. Conservation and multiplication of an endangered medicinal plant – Caralluma arabica

© 2014 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, ••, pp. ••–••

86.

87.

88.

89.

90.

91.

92.

93.

94. 95.

96.

97.

– using tissue culture. Planta Med 2011; 77: PB49. Rizwani GH Phytochemical and biological studies on medicinal herbs, C. tuberculata and C. edulis. A thesis submitted to the University of Karachi for the Degree of Doctor of Philosphy, Department of Pharmacogonosy, Faculty of Pharmacy, and University of Karachi. 1991. Hussain W et al. Tradable and conservation status of medicinal plants of Kurram Valley, Parachinar, Pakistan. J Appl Pharma Sci 2012; 2: 66–70. Olfield S Cactus and succulent plants-status survey and conservation action plan. IUCN/SSC. Cactus and succulent specialist group. IUCN, Gland, Switzerland and Cambridge, UK. 10+212. 1997. Shah A et al. Ethnobotanical study of medicinal plants of semi-tribal area of Makerwal & Gulla Khel (lying between Khyber Pakhtunkhwa and Punjab Provinces), Pakistan. Am J Plant Sci 2013; 4: 98–116. Azizullah A et al. Water pollution in Pakistan and its impact on public health. Environ Int 2011; 37: 479– 497. Shinwari ZK et al. Medicinal and Aromatic Plants of Pakistan (A Pictorial Guide). Kohat, Pakistan: Kohat University of Science and Technology, 2006: 492. Vinh DC, Rubinstein E. Linezolid: a review of safety and tolerability. J Infect 2009; 59: 59–74. Edward J et al. Efficacy of B-celltargeted therapy with rituximab in patients with Rheumatoid arthritis. N Engl J Med 2004; 350: 2572–2581. Deepak D et al. Plant pregnanes. Phytochemistry 1989; 23: 3255–3263. Mitsuhashi H et al. Constituents of Asclepiadaceae plants. Chem Pharm Bull 1965; 13: 1332–1340. Kommidi DR et al. Minor pregnanes from Caralluma adscendens var. gracilis and Caralluma pauciflora. Fitoterapia 2011; 82: 1039–1043. Essam A et al. Antitrypanosomal activity of some pregnane glycosides 17

Medicinal properties of genus Caralluma

98.

99.

100.

101.

102.

103.

104.

18

isolated from Caralluma species. Phytomedicine 2009; 16: 659–664. Al-Massarani SM et al. Acylated pregnane glycosides from Caralluma sinaica. Phytochemistry 2012; 79: 129–140. Rizwani GH et al. Pregnane glycosides from Caralluma tuberculata. Nat Prod Lett 1993; 2: 97–104. Khare AK et al. Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, ‘Gurmar’) in normal and diabetic persons. Indian J Physiol Pharmacol 1983; 27: 257–258. Deepak D et al. Pregnane glycosides. Chem Org Nat Prod 1995; 71: 169– 325. Piaz FD et al. Electrospray ionization mass spectrometry for identification and structural characterization of pregnane glycosides. Rapid Commun Mass Spectrom 2005; 19: 1041– 1052. Qiu SX et al. Acylated C-21 steroidal bisdesmosidic glycosides from Caralluma umbellata. Phytochemistry 1997; 46: 333–340. Masayoshi O et al. Five new steroidal glycosides from Caralluma dalzielii. Helv Chim Acta 2007; 90: 63–71.

Muhammad Adnan et al.

105. Rehman S et al. Ethnobotanically important plants of Humzoni, Nwa, Kpk, Pakistan. Int J Herb Med 2013; 1: 89–101. 106. Kamil M et al. Separation of flavonoids from Caralluma arabica using high-speed counter-current chromatography. J Pharm Pharmacol 2000; 52: 265. 107. Castro VA et al. A 3, 4-secotriterpene from Caralluma buchardii. Phytochemistry 1980; 19: 2210– 2212. 108. Abdur R et al. Phytochemical, phytotoxic and antioxidant profile of Caralluma tuberculata N. E. Brown. Wudpecker J Pharm Pharmacol 2013; 2: 21–25. 109. Harbourne JB. Phytochemical Methods, A Guide to Modern Techniques of Plant Analysis. London: Chapman and Hall, 1984. 110. Newman DJ et al. The influence of natural products upon drug discovery. Nat Prod Res 2000; 17: 215– 234. 111. Person AK et al. Fungal infections in transplant and oncology patient. Infect Dis Clin North Am 2010; 24: 439–459.

112. Loudon KW et al. Kitchens as a source of Aspergillus niger infection. J Hosp Infect 1996; 32: 191–198. 113. Parekh J, Chanda SV. In vitro antimicrobial activity and phytochemical analysis of some Indian medicinal plants. Turk J Biol 2007; 31: 53–58. 114. Raziq N et al. Correlation of the antioxidant capacity with the phenolic contents of hypericummonogynum and hypericumperforatum. Afr J Pharm Pharmacol 2011; 5: 1872– 1876. 115. Shashoua VE, Hesse GW. N-docosahexaenoyl, 3 hydroxytyramine: a dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite. Life Sci 1996; 58: 1347–1357. 116. Astell KJ et al. A pilot study investigating the effect of Caralluma fimbriata extract on the risk factors of metabolic syndrome in overweight and obese subjects: a randomised controlled clinical trial. Complement Ther Med 2013; 21: 180–189. 117. Kamalakkannan S et al. Effect of Caralluma fimbriata extract on 3T3-L1 pre-adipocyte cell division. Food Nutr Sci 2011; 2: 329–336.

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A review on ethnobotany, phytochemistry and pharmacology of plant genus Caralluma R. Br.

Caralluma is a xerophytic genus used as traditional medicine for the treatment of diabetes, inflammation, leprosy, obesity and rheumatism. Objectives ...
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