Terminalia

Scientific Name(s): Terminalia arjuna Wight & Arn., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz. Family: Combretaceae.

Common Name(s): Arjuna , Axjun , Argun kahua , Kumbuk , ( T. arjuna ); Behada , Bahera ( Bahira ), Balera ( T. bellirica ); Hara , Harada , Hirala , Myrobalan , Haritaki ( T. chebula ); Bala harade ( T. chebula black variety).

Uses

Terminalia has been evaluated to a limited extent for its cardiovascular properties as well as for its role in cancer therapy. Hepatoprotective, cholesterol-reducing, and antioxidant effects have been described. However, there is limited clinical information is too limited to recommend Terminalia for any use.

Dosing

Clinical studies have been conducted in coronary heart disease using T. arjuna bark extract at doses of 500 mg every 8 hours for up to 3 months. Dosages for other Terminalia species have not been clinically defined.

Contraindications

Contraindications have not been determined.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

None well documented.

Adverse Reactions

Research suggests extracts of T. arjuna are well tolerated. Information on other species is limited.

Toxicology

Information is limited.

Botany

The Terminalia species are evergreen trees. T. arjuna reaches approximately 30 m in height, has light-yellow flowers, and cone-shaped leaves. T. bellirica has clustered oval leaves and greenish, foul-smelling flowers with brown, hairy fruit about the size of walnuts. T. chebula grows approximately 21 m in height with white flowers and small, ribbed fruits. T. arjuna is used primarily for its bark, whereas in other Terminalia species, the fruit is used. 1 , 2 , 3 , 4 , 5

History

Arjuna bark has been used in Indian medicine for at least 3,000 years as a remedy for heart ailments, and T. chebula has been used as a digestive aid. This species, referred to as “king of medicine” by Tibetans, is often depicted in the extended palm of Buddha. A traditional Ayurvedic herbal combination dating back 5,000 years is a mixture of 3 herbs, two of which are Terminalia species: T. bellirica (for health-harmonizing qualities), T. chebula (to normalize body balance), and Emblica officinalis (for vitamin C content; see separate Emblica monograph). 3 , 4

Chemistry

Tannins, flavonoids, and sterols have all been identified in these Terminalia species. Other constituents include amino acids, fructose, resin, and fixed oils.

In varying compositions, anthraquinones, gallic acid, chebulinic and chebulagic acid, ellagic and ethaedioic acid, and terpinenes and terpinenols have been described for the T. chebula species. 4 , 5 , 6 , 7

T. arjuna roots contain the oleanane triterpenoids arjunic acid, arjungenin, glycosides, and cardenolide. 8 , 9 Anthraquinones and gallic acid have also been isolated from the T. bellirica species. 4 , 10

Uses and Pharmacology

Antimicrobial

T. chebula has been most extensively evaluated for antimicrobial properties, but no clinical application has been identified for any of the Terminalia species.

Activity has been demonstrated against Staphylococcus aureus (including methicillin-resistant strains), 11 , 12 , 13 Salmonella typhi , 14 Clostridium perfringens , Escherichia coli , 7 certain dermatophytes, 15 and Candida species. 15 , 16 , 17 Aqueous, methanol, butanol, and other fractions have all been evaluated and have somewhat different properties.

T. bellirica has demonstrated antimicrobial activity in vitro, including activity against methicillin-resistant S. aureus . 12 , 18 , 19

Certain Terminalia species demonstrate in vitro antiviral activity. 20 , 21 , 22 , 23 , 24

Cancer

T. chebula (dried fruit) 25 and T. arjuna (bark) 26 , 27 have been investigated for potential activity against certain human cancer cell lines. Growth inhibition and cytotoxic effects are apparent, with concentration-dependent apoptosis and cell necrosis as the proposed mechanisms.

Cardiovascular
Animal data

Experiments in rats with T. arjuna and extracted arjunolic acid have demonstrated an antiplatelet and anticoagulant action similar to that of acetylsalicylic acid. 28 , 29

In dogs, T. arjuna bark extract caused dose-dependent hypotension, suggesting adrenergic beta-2 receptor agonist activity. 30

Clinical data

Clinical studies have been conducted in coronary heart disease using T. arjuna bark extract at doses of 500 mg every 8 hours.

Statistically significant reduction in angina and improved diastolic function was shown in patients with ischemic mitral regurgitation at 1 and 3 months with T. arjuna . 31 Effects similar to treatment with isosorbide mononitrate 40 mg daily were demonstrated in patients with chronic stable angina given T. arjuna bark extract. Reduction in the frequency of angina and improved treadmill exercise test parameters were shown. 32

Brachial artery endothelial dysfunction was improved after 2 weeks of T. arjuna bark extract versus placebo in young male smokers. 33

Other uses
Anti-inflammatory

Chebulagic acid extracted from T. chebula suppressed the onset and progression of collagen-induced arthritis in mice. 34

Antioxidant

Experiments in mice 35 , 36 and human tissue 7 , 37 as well as one clinical trial 38 have demonstrated antioxidant action of T. arjuna and T. chebula species.

Cholesterol

In combination with E. officinalis and T. chebula , T. bellirica reduced cholesterol-induced atherosclerosis in rabbits. 39 In another report, T. bellirica reduced lipid levels in hypercholesterolemic animals. 40 A reduction in cholesterol in humans has also been reported with T. arjuna bark extract at a dosage of 500 mg daily. 38

Hepatoprotection

In clinical trials and animal experiments, T. bellirica 10 and T. arjuna , alone 35 as well as in combination, 41 exhibited hepatoprotective effects.

Dosage

Clinical studies have been conducted in coronary heart disease using T. arjuna bark extract 500 mg every 8 hours for up to 3 months. 31 , 32 , 33 Dosages for other Terminalia species have not been clinically defined.

Pregnancy/Lactation

Because information regarding safety and efficacy in pregnancy and lactation is lacking, avoid use. One source cautions against taking T. bellirica and T. chebula during pregnancy. 4

Interactions

None well documented. Potentiation of the anticoagulant effect of warfarin and other anticoagulants might be expected because T. arjuna bark extract exhibits antiplatelet and anticoagulant action similar to that of aspirin. 28

Adverse Reactions

Research suggests extracts of T. arjuna are well tolerated. Adverse reactions similar to those seen with placebo (constipation, headache, abdominal discomfort, body ache) were described in one clinical trial, 32 while mild gastritis was noted in another. 31 T. arjuna also exhibits antiplatelet and anticoagulant activity. 28

Information on other species is limited.

Toxicology

Data are not well documented.

Bibliography

1. Terminalia . USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , 9 May 2007). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Terminalia arjuna . USDA, ARS, National Genetic Resources Program. Germplasm Resources Information Network—(GRIN) [Online Database]. National Germplasm Resources Laboratory, Beltsville, Maryland. http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?80199 (26 February 2007).
3. Evans WC . Trease and Evans' Pharmacognosy , 14th ed. London: WB Saunders; 1996:493.
4. Chevallier A . Encyclopedia of Medicinal Plants . New York, NY: DK Publishing; 1996:141,273.
5. Bruneton J . Pharmacognosy, Phytochemistry, Medicinal Plants . Hatton CK, trans. Paris, France: Lavoisier; 1995:333.
6. Xie P, Chen S, Liang Y, Wang X, Tian R, Upton R . Chromatographic fingerprint analysis—a rational approach for quality assessment of traditional Chinese herbal medicine . J Chromatogr A . 2006;1112:171-180.
7. Kim HG, Cho HG, Jeong EY, Lim JH, Lee SH, Lee HS . Growth-inhibiting activity of active component isolated from Terminalia chebula fruits against intestinal bacteria . J Food Prot . 2006;69:2205-2209.
8. Yadav RN, Rathore K . A new cardenolide from the roots of Terminalia arjuna . Fitoterapia . 2001;72:459-461.
9. Pawar RS, Bhutani KK . Effect of oleanane triterpenoids from Terminalia arjuna —a cardioprotective drug on the process of respiratory oxyburst . Phytomedicine . 2005;12:391-393.
10. Anand KK, Singh B, Saxena AK, Chandan BK, Gupta VN, Bhardwai V . 3,4,5-Trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits of Terminalia bellirica -bioassay guided activity . Pharmacol Res . 1997;36:315-321.
11. Sato Y, Oketani H, Singyouchi K, et al . Extraction and purification of effective antimicrobial constituents of Terminalia chebula RETS against methicillin-resistant Staphylococcus aureus . Biol Pharm Bull . 1997;20:401-404.
12. Aqil F, Kahn MS, Owais M, Ahmad I . Effect of certain bioactive plant extracts on clinical isolates of beta-lactamase producing methicillin resistant Staphylococcus aureus . J Basic Microbiol . 2005;45:106-114.
13. Bonjar GH . Inhibition of Clotrimazole-resistant Candida albicans by plants used in Iranian folkloric medicine . Fitoterapia . 2004;75:74-76.
14. Rani P, Khullar N . Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against multi-drug resistant Salmonella typhi . Phytother Res . 2004;18:670-673.
15. Vonshak A, Barazani O, Sathiyamoorthy P, Shaler R, Vardy D, Golan-Goldhirsh A . Screening South Indian medicinal plants for antifungal activity against cutaneous pathogens . Phytother Res . 2003;17:1123-1125.
16. Bonjar GH . Antibacterial screening of plants used in Iranian folkloric medicine . Fitoterapia . 2004;75:231-235.
17. Dutta BK, Rahman I, Das TK . Antifungal activity of Indian plant extracts . Mycoses . 1998;41:535-536.
18. Ahmad I, Mehmood Z, Mohammad F . Screening of some Indian medicinal plants for their antimicrobial properties . J Ethnopharmacol . 1998;62:183-193.
19. Phadke SA, Kulkarni SD . Screening of in vitro antibacterial activity of Terminalia chebula , Eclapta alba , and Ocimum sanctum . Indian J Med Sci . 1989;43:113-117.
20. Shiraki K, Yukawa T, Kurokawa M, Kageyama S . Cytomegalovirus infection and its possible treatment with herbal medicines [in Japanese] . Nippon Rinsho . 1998;56:156-160.
21. Yukawa T, Kurokawa M, Sato H . Prophylactic treatment of cytomegalovirus infection with traditional herbs . Antiviral Res . 1996;32:63-70.
22. Kurokawa M, Nagasaka K, Hirabayashi T, et al . Efficacy of traditional herbal medicines in combination with acyclovir against herpes simplex virus type I infection in vitro and in vivo . Antiviral Res . 1995;27:19-37.
23. el-Mekkawy S, Meselhy MR, Kusumoto IT, Kadota S, Hattori M, Namba T . Inhibitory effects of Egyptian folk medicines on human immunodeficiency virus (HIV) reverse transcriptase . Chem Pharm Bull . 1995;43:641-648.
24. Badmaev V, Nowakowski M . Protection of epithelial cells against Influenza A virus by a plant derived biological response modifier Ledretan-96 . Phytother Res . 2000;14:245-249.
25. Saleem A, Husheem M, Härkönen P, Pihlaja K . Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit . J Ethnopharmacol . 2002;81:327-336.
26. Nagpal A, Meena LS, Kaur S, Grover IS, Wadhwa R, Kaul SC . Growth suppression of human transformed cells by treatment with bark extracts from a medicinal plant, Terminalia arjuna . In Vitro Cell Dev Biol . 2000;36:544-547.
27. Sivalokanathan S, Vijayababu MR, Balasubramanian MP . Effects of Terminal arjuna bark extract on apoptosis of human hepatoma cell line HepG2 . World J Gastroenterol . 2006;12:1018-1024.
28. Sumitra M, Manikandan P, Kumar DA, et al . Experimental myocardial necrosis in rats: role of arjunolic acid on platelet aggregation, coagulation and antioxidant status . Mol Cell Biochem . 2001;224:135-142.
29. Tariq M, Hussain SJ, Asif M, Jahan M . Protective effect of fruit extracts of Emblica officinalis (Gaertn.) and Terminalia bellirica (Roxb.) in experimental myocardial necrosis in rats . Indian J Exp Biol . 1977;15:485-486.
30. Nammi S, Gudavalli R, Babu BS, Lodagala DS, Boini KM . Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized dogs . BMC Complement Altern Med . 2003;3:5.
31. Dwivedi S, Aggarwal A, Agarwal MP, Rajpal S . Role of Terminalia arjuna in ischemic mitral regurgitation . Int J Cardiol . 2005;100:507-508.
32. Bharani A, Ganguli A, Mathur LK, Jamra Y, Raman PG . Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjun a with isosorbide mononitrate . Indian Heart J . 2002;54:170-175.
33. Bharani A, Ahirwar LK, Jain N . Terminalia arjuna reverses impaired endothelial function in chronic smokers. Indian Heart J . 2004;56:123-128.
34. Lee SI, Hyun PM, Kim SH, et al . Suppression of the onset and progression of collagen-induced arthritis by chebulagic acid screened from a natural product library . Arthritis Rheum . 2005;52:345-353.
35. Manna P, Sinha M, Sil PC . Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders . BMC Complement Altern Med . 2006;6:33.
36. Gandhi N, Nair C . Radiation protection by Terminalia chebula : some mechanistic aspects . Mol Cell Biochem . 2005;277:43-48.
37. Na M, Bae K, Kang SS, et al . Cytoprotective effect on oxidative stress and inhibitory effect on cellular aging of Terminalia chebula fruit . Phytother Res . 2004;18:737-741.
38. Gupta R, Singhal S, Goyle A, Sharma VN . Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark and powder: a randomised placebo-controlled trial . J Assoc Physicians India . 2001;49:231-235.
39. Thakur CP, Thakur B, Singh S, et al . The Ayurvedic medicines Haritaki, Amala, and Bahira reduce cholesterol-induced atherosclerosis in rabbits . Int J Cardiol . 1988;21:167-175.
40. Shaila HP, Udupa AL, Udupa SL . Preventive actions of Terminalia bellirica in experimentally induced atherosclerosis . Int J Cardiol . 1995;49:101-106.
41. Huseini HF, Alavian SM, Heshmat R, Heydari MR, Abolmaali K . The efficacy of Liv-52 on liver cirrhotic patients: a randomized, double-blind, placebo-controlled first approach . Phytomedicine . 2005;12:619-624.

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