Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

Chapter 4

Phytochemical and Pharmacological Review of Selected Plants: Adhatoda zeylanica Nees and Embelia ribes Burm.f.
4.1 INTRODUCTION It is always necessary to carry out thorough survey of scientific literature to determine what is known about the study and to eliminate unnecessary duplication of research. To achieve these objectives, a strategy was developed several years ago, which comprises of (i) A survey of information on the use of a particular plant as well as its preparations in traditional medicine (i.e., field studies of classical texts), (ii) A survey of modern scientific literature and (iii) experimental research which is projected on the basis of data collected in the preceding phases (Simons, 1989). In this section, an overview of Adhatoda zeylanica and Embelia ribes with respect to botany, traditional and contemporary use, pharmacological properties and phytochemistry are given. 4.2 ADHATODA ZEYLANICA NEES 4.2.1 Botanical identity Adhatoa zeylanica Medic. Syn. Adhatoda zeylanica Nees; Family: Acanthaceae 4.2.2 Distribution Throughout India upto an altitude of 1300 m 4.2.3 Classical names Vasa, Vasaka, Simhasya, Shimhaparna, Tamra, Vaiska, Vajidanta, Atarusha, Atarushka, Shimhika, Vrisha 4.2.4 Vernacular names English Hindi Bengali Gujrati Kannada Malayalam : Vasaka : Arusa, Bakas, Adusa, Rusa : Basak, Bakas : Aradusi, Adulso : Adusoge, Kurchigida, Pavate, Bansa : Adalodakam 55

Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

Marathi Punjabi Tamil Telugu Kashmiri Konkani Oriya

: Adulsa : Bhekkar : Adhatodai, Pavettai : Addasaramu : Bahekar, Baikar, Bansuth, Babading : Adusogae : Arusa, Basung

4.2.5 Botanical description Perennial, evergreen shrub, 1.2 2.5 m high. Leaves elliptic- lanceolate or ovate lanceolate, entire, leathery. Flowers white with red or yellow barred throats, in spikes with large bracts. Capsules clavate, longitudinally channelled, 1.9 - 2.2 cm long. Seeds globular. 4.2.6 Parts used Root, leaf, flower, fruit are used for therapeutic use. 4.2.7 Traditional uses A. zeylanica has been most frequently used for the treatment of respiratory complaints and for cough, asthma and colds (Maikhuri and Gangwar, 1993). It is used as an expectorant, bronchodilator and to liquefy sputum (Dymock et al., 1890; Kirtikar and Basu, 1975; Nadkarni, 1976; Pushpangadan et al., 1995; Salalamp et al., 1996). A. zeylanica as an expectorant and antispasmodic agent was described and an alkaloid with a bitter taste was identified and named vasicine (Dymock et al., 1890). Jain et al (1994) observed that the Neterhat people in Bihar used a decoction of the leaves to stimulate and heal before and after delivery. Nath et al (1997) observed the use of A. zeylanica as an abortifacient in the Gora village of Lucknow, Uttar Pradesh. They found that 70% of the pregnant women use the leaves of A. zeylanica to induce abortion. The macerated roots of the Vasak (A. zeylanica) are applied on the pubic region and the vagina to help parturition (Pathak 1970). It is also described in the Gazetteer of Bombay State (Agharkar, 1953) and by Kirtikar and Basu, (1975) that root facilitates the expulsion of foetus. Pushpangadan et al. (1995) stated the use of the whole plant of A. zeylanica for treating impotence and sexual disorders. The use of A. zeylanica leaves for checking postpartum haemorrhage was also mentioned. The leaves were toxic to all forms of lower life and have insecticidal effect (Dymock et al., 56

Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

1890; Drieberg, 1935; Agharkar, 1953; Agarwal, 1986). It was used in intermittent, typhus fevers, febrifuge and diphtheria (Wren, 1932). It was also used for stomach catarrh with constipation, rheumatism, gout, and urinary stone (Madaus, 1938). Decoction of leaves is used for fever (Jain, 1965). Ash of leaves, smoke from leaf and wood are used for cough and asthma (Shah and Joshi, 1971). Leaves and seeds are used for asthma, cough, colds dysentery and diarrhea (Jain and Verma, 1981). Externally warmed leaves used for rheumatic pains and dislocation of joint (Rao and Jamir, 1982). Yellow leaves are used for cough (Lal and Yadav, 1983). Decoction and ash of leaves is used for bronchial complaints such as cough, asthma, tuberculosis and antipyretic (Jain and Puri, 1984; Bhattarai, 1989). Leaf juice orally is used for coughs, fever, malarial fever (John, 1984). Plant juice is used for cough, asthma and bronchitis (Kapur and Sarin, 1984). Leaf powder is used for cough and jaundice (Reddy et al, 1988). Leaf powder boiled in sesame oil is used to stop bleeding, ear aches, and pus from ears (Reddy et al., 1989). Leaf extract is used for bronchial troubles (Sharma et al., 1992). Root decoction is used for gonorrhoea (Siddiqui and Husain, 1993). Water extract of leaf is used to relieve acidity (Manandhar, 1993). Leaf is used for urinary trouble. 4.2.8 Chemistry Leaves of Vasaka contains pyrroloquinazoline alkaloids, chiefly vasicine (1,2,3,9Tetrahydropyrrolo[2,1b]quinazolin3ol, C11H12N2O) (Haq et al., 1967) and vasicinone (3hydroxy2,3-dihydropyrrolo[2,1b]quinazolin9(1H)one, C11H10N2O2) (Amin and Mehta, 1959). It also contains adhatodine, anisotine, vasicoline and vasicolinone (Johne et al., 1971). -sitosterol, tritricontane and vasicinine (Haq et al., 1967), vasicinol identical with 6-hydroxypeganine; 6-hydroxypeganine isolated from leaves. A quinazoline alkaloid isolated from leaves and characterised as 1,2,3,9,-tetrahydro-5-methoxypyrrolo[2,1-b]quinazolin-3-ol (Chowdhury & Bhattacharyya, 1985), adhavasinone isolated and characterised (Chowdhury & Bhattacharyya, 1987).

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(1) Vasicine: 1,2,3.9 Tetrahydropyrrolo[2,1-b] quinazolin-3-ol (Haq et al., 1967) (2) Vasicinone: 2,3-(- hydroxytrimethylene)-4-quinazolone (Amin and Mehta, 1959)

N
1,2,3,9,-tetrahydro-5-methoxypyrrolo[2,1-b]quinazolin-3-ol R = H,H

N OH OMe

Adhavasinone R=O

(3) 1,2,3,9,-tetrahydro-5-methoxypyrrolo[2,1-b]quinazolin-3-ol (Chowdhury & Bhattacharyya, 1985) (4) Adhavasinone (Chowdhury & Bhattacharyya, 1987)

Adhatodine R = H,H, RI = H, RII = COOMe, RIII = NHMe Anisotine R = O, RI = H, RII = COOMe, RIII = NHMe Vasicoline R = H,H, RI = NMe2, RII, RIII = H Vasicolinone R = O, RI = NMe2, RII, RIII = H

(5) Adhatodine (Johne et al., 1971) (6) Anisotine (Johne et al., 1971) (7) Vasicoline (Johne et al., 1971) (8) Vasicolinone (Johne et al., 1971)

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Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

4.2.9 Pharmacology Essential oil from the leaves showed smooth muscle relaxant activity in the isolated guinea-pig tracheal chain (DCruz et al., 1979). Methanolic extract from the plant has been shown to possess anti-allergic and anti-asthmatic activities in guinea-pig after inhalation or intragastric administration at doses of 6 mg per animal or 2.5 gm/kg, respectively (Muller et al., 1993). Ethanolic extract from the leaves showed hypoglycaemic activity after oral administration in rats and rabbits (Modak and Rao, 1966; Dhar et al., 1968). The water extract was shown to be active against the microbial flora isolated from patients with gingivitis (Patel and Venkata-Krishna-Bhatt, 1984). Vasicine showed bronchodilatory activity both in vitro and in vivo. Although vasicinone, the main metabolite of vasicine, which is also present in A. zeylanica extract, showed bronchoconstriction in vivo. The two alkaloids in combination showed a bronchodilatory activity both in vitro and in vivo (Atal, 1980). Vasicine was found to have uterotonic activity in different species including human beings. It was shown that the effect was influenced by the degree of priming of the uterus by estrogens. Vasicine initiated rhythmic contractions of human myometrial strips from both non-pregnant and pregnant uteri. The effect was comparable with that of oxytocin and methergin (Atal, 1980). The antiinflammatory activity of the methanol extract, the non-alkaloid fraction, the saponins and the alkaloids was evaluated by the modified hen's egg chorioallantoic membrane test. Alkaloid fraction showed potent activity at a dose of 50 g/pellet (Chakraborty and Brantner, 2001). Leaf showed significant hepatoprotective effect at doses of 50-100 mg/kg, p.o., on liver damage induced by D-galactosamine in rats (Bhattacharyya et al., 2005). Adhatoda zeylanica extract was shown to have a good antitussive activity in anaesthetized guinea pigs and rabbits and in unanaesthetized guinea pigs. Intravenously, it was 1/20-1/40 as active as codeine on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of Adhatoda zeylanica was similar to codeine against coughing induced by irritant aerosols (Dhuley, 1999). Leaf extracts orally in rats were 100% abortive at doses equivalent to 175 mg/kg of starting dry material (Nath et al., 1992). Ethanolic extract of leaf showed 60-70% anti-implantation activity in female albino rats (Prakash et al., 1985). Oral administration of A. zeylanica leaf extract (800 mg /kg body weight) in Swiss albino mice prior to whole body irradiation showed a significant protection in terms of survival percentage and hematological parameters

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Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

(Kumar et al., 2005). Leaf powder showed considerable degree of anti-ulcer activity in experimental rats in ethanol-induced, and pylorus ligation plus aspirin-induced models (Shrivastava et al., 2006). It also showed wound healing (Bhargava and Singh, 1988), antiallergic (Chatterjee, 1999) and antibacterial activity (Brantner and Chakraborty, 1998). 4.2.10 Therapeutic evaluation Clinical trials of a drug containing vasicine and vasicinone have not revealed any side effects while trating bronchial asthma. Drug is known to possess abortifacient activity and hence not to be used during pregnancy. 4.3 EMBELIA RIBES BURM. F. 4.3.1 Botanical identity Embelia ribes Burm. f., Family: Myrsinaceae 4.3.2 Distribution It is found throughout India up to an altitude of 1600 m, from Central Himalaya to Konkan, Deccan, Western Ghats and South India. 4.3.3 Classial names Vidanga, Krimighna, Chitratandula, Jantunashana, Vella, Amogha, Kitashatru, Kitari, Krimijit, Krimiripu, Krimihara, Krimihrit, Jantughna, Jantuhrit. 4.3.4 Vernacular names English Hindi Bengali Gujrati Kannada Malayalam Marathi Punjabi Tamil Telugu Assam : Embelia : Vayavidanga, Bhabhiranga, Baberang, Wawrung, Vayvidamg : Vidang, Biranga, Bhai-birrung : Vavading, Vayavadang, Vyvirang : Vayuvilanga, Vayuvidanga : Vizhalari, Vilal : Vavding, Karkannie : Babrung, Vavaring : Vayuvilangam, Vayuvidangam, Vellal : Vayuvidangalu, Vayu-vilamgam, Vayuvidangamu, Vidanga : Vidang

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Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

Kashmiri Oriya

: Babading : Bidanga, Vidanga, Baibidanga

4.3.5 Botanical description A large, scandant shrub with long slender, flexible, terete branches; bark studded with lenticles. Leaves simple, alternate, elliptic-lanceolate, gland dotted, short and obtusely acuminate, entire, shiny above. Flowers small, white or greenish, in both terminal and axillary panicles. Fruits globose, wrinkled or warty, dull red to nearly black, a short pedicel often present, usually one seeded; seeds globose. 4.3.6 Parts used Fruit, root, leaf 4.3.7 Traditional uses The dried fruit was considerd anthelmintic, astringent, carminative, alternative and stimulant. It has been employed in India, since ancient times, as anthelmintic and is administered as powder, usually with milk , followed by a purgative. It was effectice in the treatment of ascariasis, and for this purpose it was better than Santonin and as good as Oil of Chenopodium (Anonymus, 1952). 4.3.8 Chemistry

(1) Embelin : 2,5-dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-dione (Hao et al., 2005)

OH

CH2(CH2)23CH2OC(CH2)5CH=CHCH(CH2)9CH3

(2) Embeliaribyl ester : n-pentacosanyl-n-nonadeca-7'-en-9'-alpha-ol-1'-oate

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Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

OH

H3C(H2C)13HC(H2C)2H2CO H O

CH2 O

OCH2(CH2)3CH3

(3) Embelinol : 3-(4"-hydroxyoctadecanyloxy)-p-quinonyl-5-methylene-8-(10pentanyloxy)-p-quinone

(4) Embeliol : 1,2,4,5-tetrahydroxy 3-undecanyl benzene

(5) Vilangin: methylenebis-(2,5-dihydroxy-4-undecyl-3,6-benzoquinone (Venkateswarlu & Bheemasankara Rao, 1961).

(6) Potassium embelate, 2,5-dihydroxy, 3-undecyl-1, 4-benzoquinone, from Embelia ribes Burm. (Johri et al., 1990).

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Phytochemical and Pharmacological Review of Adhatoda zeylanica and Embelia ribes

4.3.9 Pharmacology Aqueous E. ribes extract showed a significant blood glucose and blood pressure lowering potential. The same extract increased endogenous antioxidant defense against free radicals produced under hyperglycaemic conditions and thereby, protected the pancreatic -cells against loss in streptozotocin induced diabetic rats (Bhandari and Ansari, 2008). Ethanolic E. ribes extract treatment increased the antioxidant defense against methionine-induced hyperhomocysteinemia and oxidative stress in brain (Ansari and Bhandari, 2008). Aqueous E. ribes extract (100 mg/kg) pretreatment orally for 40 days in isoproterenol (ISO)-treated rats significantly decreased the heart rate, systolic blood pressure, increased levels of serum lactate dehydrogenase, serum creatine kinase and myocardial lipid peroxides and significantly increased the myocardial endogenous antioxidants (glutathione, superoxide dismutase and catalase) levels. Thus E. ribes extract pretreatment improved myocardial injury and enhanced the antioxidant defense against ISO-induced myocardial infarction in rats and exhibited cardioprotective property (Bhandari et al., 2008). Chronic treatment with ethanolic E. ribes extract enhanced the antioxidant defense against MCAO- induced focal cerebral ischemia in rats and exhibited neuroprotective activity (Ansari et al., 2008). Embelin, major compound present in the E. ribes showed good wound healing property (Kumara Swamy et al., 2007). Extract of berries showed antifertility activity in rats and also anti-oestrogenic activity (Prakash & Mathur, 1979). It also showed encouraging antifertility activity. Embelin was found to be a NF-kappaB blocker and potential suppressor of tumorigenesis (Ahn et al., 2007). Embelin showed chemopreventive effect against DENA/PB-induced hepatocarcinogenesis in Wistar rats (Sreepriya et al., 2005). Embelin showed significant antibacterial activity mostly at the higher concentration (100 mg). The inhibition was highly significant against Staphylococcus aureus, Streptococcus pyogenes, Shigella flexneri, S. sonnei and Pseudomonas aeruginosa; moderate against Salmonella typhi, S. boydii and Proteus mirabilis (Chitra et al., 2003). Methanol and aqueous extract of E. ribes showed moderate activity against multi-drug resistant Salmonella typhi (Rani and Khullar, 2004). Potassium embelate showed potent centrally acting analgesic activity (Zutshi et al., 1989). Embelin showed antispermatogenic effect both in vivo albino rats and in vitro (Gupta et al., 1989). Embelin altered the testicular histology and glycogen, gametogenic counts and accessory sex gland fructose at the dose levels 0.3, 0.4 and 0.5 mg/kg body weight

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administered subcutaneously for 35 days. The compound showed antiandrogenic activity (Agrawal et al., 1986). 4.3.10 Therapeutic evaluation Clinical studies were conducted with alcoholic and queous extracts of E. ribes fruits on 40 children infected by ascarides. Alcoholic extract was found effective in 80 percent cases, while aqeous extract cured 55 percent cases, rendering stools free from ova. No toxic effects were observed during and after tratment. Fruits of Embelia ribes, when administered in doses of 200 mg/kg to patients of worm infestation, produced good results. Marked improvement was observed in cases of tape worm, giardia N. nana. A single dose upto a maximum of 8 gm was sufficient. Worms were expelled within 6 to 24 hours of taking the drug. The drug was well tolerated and safe for use. School children (5-12 years) suffering from various helminth diseases were treated with the Ayurvedic praparation, Kuberakshadi yoga, in a dose of 200 mg per kg body wt. in two divided doses. The drug was found effective against Enterobium vermicularis and Ascaris lumbricoides. Kuberakshadi yoga contained Caesalpinia bonducella, Embelia ribes, Ptychotis sp., Myristica fragrans, Caryophyllum aromaticum and Curcuma cyminum. Pippalyadi yoga, a composite drug containing Piper longum, Embelia ribes and borax in equal amount, was invesigated in 254 women covering 4694 cycles for contaceptive property. Oral admimistration of drug in a dose of 1 gm/day gave very good results. Drug failure was observed only in 4 womwn. Preganancy due to drug omission was found in 26 women. Minor side effects were observed in 17 cases. Ferility appeared normal after discontinuation of the drug. Clinical trials were conducted with Vidangadi yoga (a herbal preparation containing Embelia ribes seeds, Hibiscus rosa-sinensis flowers and Ferula foetida oleo-gum resin) for its antifertility activity. The drug was found to be vey effective and showed no toxic effects. AC-4, a composite drug containing Embelia ribes, Laccardia lacca, Areca catechu and Saraca asoca in equal parts, when administered orally (1 gm/day in twi dividwd doses) to 281 women for 15 days (4th day of menstrual cycle to 18th day) exhibited good

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contraceptive activity. There was no pregnancy due to drug failure after 10th cycle. No toxic symptoms or severe side effects were noticed. Powders of Vidanga and Tankana in a dose of 2 gm twice a day, after meals, were administered in 150 fertile women for 6 months. 58 % of women were benefitted who followed the medication for six months continuously and no pregnancy was recorded for 2 years of follow-up. However, it was noted that cycle-wise result was 80 % successful. It was concluded that Tankana, Vidanga and Pippali Churna, administered for 5 days, can be used for 6 months to prevent pregnancy for 24 months. Solid extract prepared from the decoction of Holarrhena antidysenterica (bark and seeds), Berberis aristata (wood), Embelia ribes (fruit), Cyperus rotundus (tuber), Aegle marmelos (fruit pulp) and Butea monosperma (seeds), in a clinical trial on 25 patients of diarrhoea and dynttery, showed cure rate of 80 percent with an average 3.3 days treatment, without any toxic effect. Gasozyme syrup (indigenous herbal drug, containing Carica papaya, Carum copticum, Coriandrum sativum, Peucedanum graveolens, Atropa belladona, Aegle marmelos, Piper nigrum and Embelia ribes seeds) was administered orally (2 teaspoonfull twice a day after meals for months) to 40 patients of gastritis. Eight cases (20 %) were completely relieved of symptoms, 16 cases showed marked improvement and 10 showed satisfactory improvement.
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ischemia/reperfusion-induced Pharmacology 22(3), 305-14 oxidative stress in rats. Fundamental & Clinical

Bhandari U, Ansari MN (2008) Antihyperglycaemic activity of aqueous extract of Embelia ribes Burm in streptozotocin-induced diabetic rats. Indian Journal of Experimental Biology 46(8), 607-13 Bhandari U, Ansari MN, Islam F (2008) Cardioprotective effect of aqueous extract of Embelia ribes Burm fruits against isoproterenol-induced myocardial infarction in albino rats. Indian Journal of Experimental Biology 46(1), 35-40 Bhargava MK, Singh H (1988) Evaluation of Adhatoda vasica as a wound healing agent in buffaloes: Clinical, mechanical and biochemical studies. Indian Veterinary Journal 65, 33-38 Bhattacharyya D, Pandit S, Jana U, Sur TK (2005) Hepatoprotective activity of Adhatoda vasica aqueous leaf extract on D-galactosamine-induced liver damage in rats. Fitoterapia 76, 223-5 Bhattarai NK (1989) Traditional phytoterapy among the Sherpas of Helambu, Central Nepal. Journal of Ethnopharmacology 27, 4554 Brantner AH, Chakraborty A (1998) In vitro antibacterial activity of alkaloids isolated from Adhatoda vasica Nees. Pharmaceutical and Pharmacological Letters 8, 137-39 Chakraborty A, Brantner AH (2001) Study of alkaloids from Adhatoda vasica Nees on their antiinflammatory activity. Phytotherapy research 15, 532-4 Chatterjee S (1999) Bronchodilatory and anti-allergic effect of PulmoFlex - A proprietary herbal formulation. Indian Journal of Physiology and Pharmacology 43, 486-90 Chitra M, Devi CS, Sukumar E (2003) Antibacterial activity of embelin. Fitoterapia 74(4), 401-3 Chowdhury BK, Bhattacharyya P (1985) A Further Quinazoline Alkaloid from Adhatoda vasica. Phytochemistry (Oxford) 24, 3080-2 Chowdhury BK, Bhattacharyya P (1987) A Further Quinazoline Alkaloid from Adhatoda vasica. Chem. Ind. 35 DCruz JL, Nimbkar AY, Kokate CK (1979) Evaluation of essential oil from leaves of Adhatoda vasica as an airway smooth muscle relaxant. Indian Journal of Pharmaceutical Sciences 41, 247 Dhar ML, Dhar MM, Dhawan BN, Mehrotra BN, Ray C (1968) Screening of Indian plants for biological activity: part I. Indian Journal of Experimental Biology 6, 232247 Dhuley JN (1999) Antitussive effect of Adhatoda vasica extract on mechanical or chemical stimulation-induced coughing in animals. Journal of Ethnopharmacology 67(3), 361-65 Drieberg C (1935) Medicinal Plants of Ceylon. Columbo. pp. 302303 Dymock W, Waeden CJH, Hooper D (1890) Pharmacographia Indica, A history of the principal drugs of vegetable origin. Paul, Trech, Trubner & Co. Ltd, London. pp. 5054 Gupta S, Sanyal SN, Kanwar U (1989) Antispermatogenic effect of embelin, a plant benzoquinone, on male albino rats in vivo and in vitro. Contraception 39(3), 307-20 Hao K, Ali M, Siddiqui AW (2005) New compounds from the seeds of Embelia ribes Burm. Pharmazie 60(1), 69-71 Huq ME, Ikram M, Warsi SA (1967) Chemical Composition of Adhatoda Vasica D - Vasicine Vasicinine Beta Sito Sterol Tri Triacontane Alkaloids ii. Pakistan Journal of Scientific and Industrial Research 10, 224-5. Jain SK (1965) Medicinal plant lore of the tribals of Bastar. Economic Botany 19, 236250 Jain SP, Puri HS (1984) Ethnomedicinal plants of Jaunsar-Bawar Hills, Uttar Pradesh, India. Journal of Ethnopharmacology 12, 213222 Jain SP, Singh SC, Puri HS (1994) Medicinal plants of Neterhat, Bibar, India. International Journal of Pharmacognosy 32, 4450

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Jain SP, Verma DM (1981) Medicinal plants in the folklore of Northeast Haryana. National Academy Science Letters (India) 4, 269271 John D (1984) One hundred useful raw drugs of the Kani tribes of Trivandrum forest division, Kerala, India. International Journal of Crude Drug Research 22, 1739 Johne S, Groeger D, Hesse M (1971) New Alkaloids from Adhatoda Vasica. Helvetica Chimica Acta 54, 826-34 Johri RK, Dhar SK, Pahwa GS, Sharma SC, Kaul JL, Zutshi U (1990) Toxicity studies with potassium embelate, a new analgesic compound. Indian Journal of Experimental Biology 28, 213-7 Kapur SK, SarinYK (1984) Medico-botanic survey of medicinal and aromatic plants of Katra valley (J&K State) India. Indian Drugs 22, 410 Kirtikar KR, Basu BD (1975) An, L.C.S., Indian Medicinal Plants, vol. 3, second ed. Bishen Singh Mahendra Pal Singh, Delhi. pp. 18991902 Kumar A, Ram J, Samarth RM, Kumar M (2005) Modulatory influence of Adhatoda vasica Nees leaf extract against gamma irradiation in Swiss albino mice. Phytomedicine 12, 285-93 Kumara Swamy HM, Krishna V, Shankarmurthy K, Abdul Rahiman B, Mankani KL, Mahadevan KM, Harish BG, Raja Naika H (2007) Wound healing activity of embelin isolated from the ethanol extract of leaves of Embelia ribes Burm. Journal of Ethnopharmacology 109, 529534 Lal SD, Yadav BK (1983) Folk medicine of Kurukshetra district (Haryana), India. Economic Botany 37, 299305 Madaus G (1938) Lehrbuch der Biologischen Heilmittel, Band II. Georg Thieme, Leipzig. pp. 16811684 Maikhuri RK, Gangwar AK (1993) Ethnobiological notes on the Khasi and Garo tribes of Meghalaya, Northeast India. Economic Botany 47, 345357 Manandhar NP (1993) Herbal remedies of Surkhet district, Nepal. Fitoterapia 64, 266272 Modak AT, Rao MRR (1996) Hypoglycaemic activity of a non-nitrogenous principle from the leaves of Adhatoda vasica Nees. Indian Journal of Pharmacy 28, 105106 Muller A, Antus S, Bittinger M, Kaas A, Kreher B, Neszmelyi A, Stuppner H, Wagner H (1993) Chemistry and pharmacology of antiasthmatic Galphimia glauca, Adhatoda vasica, and Picrorhiza kurrooa. Planta Medica 59, 586587 Nadkarni KM (1976) Indian Materia Medica, With Ayurvedic, Unani-Tibbi, Siddha, Allopathic, Homeopathic, Naturopathic & Home Remedies, Appendices & Indexes. Popular Prakashan, Bombay. pp. 4043 Nagaraju N, Rao KN (1990) A survey of plant crude drugs of Rayalaseema, Andhra Pradesh, India. Journal of Ethnopharmacology 29, 137158 Nath D, Sethi N, Singh RK, Jain AK (1992) Commonly used Indian abortifacient plants with special reference to their teratologic effects in rats. Journal of Ethnopharmacology 36, 147-54 Nath D, Sethi N, Srivastava S, Jain AK, Srivastava R (1997) Survey on indigenous medicinal plants used for abortion in some districts of Uttar Pradesh. Fitoterapia 68, 223225 Patel VK, Venkata-Krishna-Bhatt H (1984) In vitro study of antimicrobial activity of Adhatoda vasica Linn. (leaf extract) on gingival inflammation-a preliminary report. Indian Journal of Medical Science 38, 7072 Pathak RP (1970) Therapeutic Guide to Ayurvedic Medicine (A Handbook on Ayurvedic Medicine). Shri Ramdayal Joshi Memorial Ayurvedic Research Institute. Publ. Series No. 1, pp. 121, 208209 Prakash AO and Mathur R (1979) Biochemical changes in the rat uterine tissue following Embelia ribes burm. Extracts. Indian Journal of Pharmacology 11, 127 - 134

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