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Terminalia

Scientific Name(s): Terminalia arjuna Wight and Arn., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula (Gaertn.) Retz.
Common Name(s): Arjuna, Axjun, Bahera (Bahira), Bala harade (T. chebula), Balera (T. bellirica), Behada, Hara, Harada, Haritaki (T. chebula), Hirala, Kahua, Kumbuk (T. arjuna), Myrobalan

Medically reviewed by Drugs.com. Last updated on May 1, 2021.

Clinical Overview

Use

Terminalia species have been evaluated to a limited extent for potential hepatoprotective, cardiovascular, cholesterol-reducing, dermatologic, antimicrobial, antioxidant, and urate-lowering effects. However, clinical trial data are lacking to recommend use for any indication.

Dosing

T. arjuna bark extract 500 mg every 8 hours (reported treatment durations, 1 to 2 weeks) has been used in clinical studies evaluating effects on cardiovascular disorders. Dosages of other Terminalia species have not been clinically defined.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

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

Interactions

None well documented.

Adverse Reactions

Extracts of T. arjuna are well tolerated. Adverse reactions similar to those with placebo (constipation, headache, abdominal discomfort, body ache) have been described. In rats, it was suggested that high amounts of T. arjuna extract could cause hepatotoxicity and hypothyroidism.

Toxicology

No data.

Scientific Family

  • Combretaceae (Indian almond)

Botany

Terminalia species are evergreen trees. T. arjuna reaches approximately 30 m in height and has light-yellow flowers and cone-shaped leaves. T. bellirica has clustered oval leaves and greenish, foul-smelling flowers with brown, hairy fruit approximately the size of a walnut. T. chebula grows approximately 21 m in height and has white flowers and small, ribbed fruits. T. arjuna is used primarily for its bark, while other Terminalia species are primarily used for their fruits. Terminalia species are found throughout the world, particularly in South Asia, Australia, and South Africa.(Bruneton 1995, Chevallier 1996, Das 2020, Evans 1996, USDA 2021, USDA 2021)

History

Arjuna bark has been used in the traditional Ayurvedic medical system 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 the "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, 2 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 Emblica monograph for more information).(Chevallier 1996, Evans 1996) This formulation is commonly known as Triphala and is used for its laxative, detoxifying, and rejuvenating effects.(Das 2020) T. arjuna has been traditionally used for its cardioprotective and hepatotoxic effects in Indian culture. T. bellirica has been used to treat diarrhea, scorpion stings, and cough. In Indian and Iranian traditional medicine, T. chebula is used to manage dementia, constipation, and diabetes.(Das 2020)

Chemistry

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

In varying compositions, anthraquinones; gallic, chebulinic, chebulagic, ellagic, and ethanedioic acids; and terpinenes and terpinenols have been described from T. chebula.(Bruneton 1995, Chevallier 1996, Kim 2006, Xie 2006)

T. arjuna roots contain the oleanane triterpenoids arjunic acid, arjungenin, glycosides, and cardenolide.(Pawar 2005, Yadav 2001) Anthraquinones and gallic acid have been isolated from T. bellirica.(Anand 1997, Chevallier 1996)

Uses and Pharmacology

Alzheimer disease

In vitro data

In vitro, T. chebula has demonstrated activity against acetylcholinesterase and butyrylcholinesterase.(Afshari 2016) This activity, combined with antioxidant and anti-inflammatory effects, suggests a possible role in Alzheimer disease.

Antidepressant effects

Animal data

In a study in Swiss mice, aqueous and ethanolic extracts of T. bellirica demonstrated antidepressant effects. Specifically, a dose-dependent reduction in immobility time in the forced swim test and tail suspension test occurred in mice receiving the aqueous extract as well as with the 100 mg/kg ethanolic extract. In addition, the 200 mg/kg aqueous extract dose and 100 mg/kg ethanolic extract dose were found to be equivalent to imipramine 15 mg/kg and fluoxetine 20 mg/kg given for 10 successive days.(Dhingra 2007)

Antihyperlipidemic activity

Animal data

In a study in rabbits with induced hypercholesterolemia, T. bellirica reduced lipid levels.(Shaila 1995) Fractions of T. arjuna at 175 mg/kg and 350 mg/kg body weight exerted effects on lipid levels to varying extents in mice with PX-407–induced hyperlipidemia.(Subramaniam 2011) In rabbits, T. arjuna reduced total cholesterol, LDL, and triglyceride levels; increased HDL levels; and reduced atherosclerotic lesions in the aorta.(Subramaniam 2011)

In Tsumura Suzuki obese diabetic (type 2 diabetes mellitus) mice, administration of a hot water extract of T. bellirica fruit suppressed the rise of glucose levels following a glucose load, decreased triglyceride levels, and was associated with reduced triglyceride content in the liver. T. bellirica also exerted inhibitory activity against pancreatic lipase. Findings from the study suggest a potential role of T. bellirica for components of metabolic syndrome.(Makihara 2012)

Clinical data

In a study of 105 successive patients with coronary heart disease, reductions in total cholesterol and LDL-C were reported with T. arjuna bark extract at a dosage of 500 mg daily.(Gupta 2001) A T. chebula extract at dosages of 250 mg and 500 mg per day was tested against placebo in subjects with type 2 diabetes; improvements in total cholesterol, HDL, LDL, and triglycerides at 12 weeks were significant compared with placebo.(Pingali 2020)

Anti-inflammatory effects

Animal data

Chebulagic acid extracted from T. chebula suppressed the onset and progression of collagen-induced arthritis in mice.(Lee 2005)

Clinical data

The effects of the proprietary product AyuFlex (a commercially available standardized aqueous extract of T. chebula fruit) on joint mobility and functional capacity were assessed in a randomized, double-blind, placebo-controlled trial of 105 overweight patients. After 84 days of treatment, AyuFlex improved various pain scores and measures of functional capacity compared with placebo, with minimal to no adverse effects.(Lopez 2017)

Antimicrobial activity

In vitro data

Activity has been demonstrated against various gram-positive and gram-negative bacteria, including Staphylococcus aureus,(Aneja 2012, Aqil 2005, Bonjar 2004, Kannan 2009, Sato 1997) Salmonella typhi,(Kannan 2009, Rani 2004) Clostridium perfringens, Escherichia coli,(Kim 2006) certain dermatophytes,(Aneja 2012) Bacillus subtilis,(Kannan 2009) Staphylococcus epidermidis,(Kannan 2009) Pseudomonas aeruginosa,(Kannan 2009) and Candida species.(Bonjar 2004, Vonshak 2003) Aqueous, methanol, butanol, and other fractions have been evaluated and have somewhat different properties.

Organic extracts of T. arjuna leaves inhibited the growth of human isolates of S. aureus, Proteus mirabilis, Acinetobacter, and P. aeruginosa. Bark extracts of T. arjuna showed inhibitory activity against these bacteria, except for P. aeruginosa.(Aneja 2012)

Experimentation in Helicobacter pylori–infected gastric epithelial cells was conducted to evaluate the effects of 24 medicinal plants indigenous to Pakistan on secretion of interleukin 8 (IL-8) and generation of reactive oxygen species (ROS) in order to assess anti-inflammatory and cytoprotective effects. Although no significant direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, T. chebula fruit extract was observed to have strong inhibitory activity on IL-8 at 50 mcg/mL and 100 mcg/mL in H. pylori–infected gastric cells.(Zaidi 2012)

Certain Terminalia species demonstrate in vitro antiviral activity against herpes simplex virus 1 (HSV1), HSV2, HIV, and influenza A.(Badmaev 2000, el-Mekkawy 1995, Kesharwani 2017, Kurokawa 1995) It has also demonstrated antiplasmodial activity in an in vitro study.(Mbouna 2018)

Antioxidant effects

Animal and in vitro data

The antioxidant effects of T. arjuna and T. chebula have been demonstrated in in vitro and animal studies.(Das 2020)

Cancer

Animal and in vitro data

T. chebula (dried fruit)(Saleem 2002) and T. arjuna (bark)(Nagpal 2000, Sivalokanathan 2006) have been investigated for activity against human cancer cell lines. Growth inhibition and cytotoxic effects are apparent, with both concentration-dependent apoptosis and cell necrosis as the proposed cytotoxic mechanisms. In Swiss mice with Ehrlich ascites carcinoma, a methanolic extract of T. arjuna leaf decreased tumor volume, weight, and viable cell count as well as extended life span of the mice.(Biswas 2012) Additionally, aqueous extracts of T. arjuna demonstrated antioxidant activity in aldo-keto reductase mice with Dalton lymphoma. Specifically, oral administration of T. arjuna increased the activity of catalase, superoxide dismutase, and glutathione transferase.(Verma 2009)

Arjunic acid isolated from the bark of T. arjuna was cytotoxic against human oral (KB), ovarian (PA 1), and liver (HepG2 and WRL-68) cancer cell lines.(Saxena 2007)

An aqueous extract of T. arjuna bark reduced buccal pouch carcinomas in hamsters, decreased lipid peroxidation, and increased antioxidant levels.(Dhanarasu 2010)

T. bellerica inhibited the growth of HepG2 human hepatocellular carcinoma and A549 lung carcinoma cells. Additionally, T. bellerica combined with cisplatin in low to medium doses in A549 cells showed synergistic and additive effects. A low-dose combination of T. bellerica and doxorubicin showed synergistic effects in HepG2 cells. All other combinations demonstrated antagonistic effects.(Pinmai 2008)

Taxol at a level of 211.1 mcg/L was produced by the endophytic fungus Pestalotiopsis terminaliae isolated from healthy, mature T. arjuna leaves.(Gangadevi 2009)

Cardiovascular effects

Animal data

Experiments in rats administered arjunolic acid extracted from T. arjuna(Sumitra 2001) and a fruit extract of T. bellirica(Tariq 1977) have demonstrated an antiplatelet and anticoagulant action similar to that of acetylsalicylic acid.

In dogs, T. arjuna bark extract caused dose-dependent hypotension, suggesting adrenergic beta-2 receptor agonist activity.(Nammi 2003)

Therapeutic and prophylactic doses of T. arjuna bark improved left ventricular function as measured by myocardial contractility index and left ventricular pressures in rats with isoproterenol-induced heart failure. Additionally, T. arjuna restored alterations in serum CK-MB levels and improved lipid levels.(Parveen 2011)

Clinical data

A statistically significant reduction in angina and improved diastolic function occurred in patients with ischemic mitral regurgitation at 1 and 3 months with T. arjuna use.(Dwivedi 2005) In a double-blind crossover study of 58 males with chronic stable angina with evidence of provocable ischemia, effects of T. arjuna bark extract 500 mg every 8 hours for 1 week were similar to those with isosorbide mononitrate 40 mg daily treatment. Reduction in the frequency of angina and improved treadmill exercise test parameters were observed.(Bharani 2002)

Brachial artery endothelial dysfunction was improved after 2 weeks of T. arjuna bark extract (500 mg every 8 hours) versus placebo in a study of young male smokers.(Bharani 2004)

In a small study of 12 patients with New York Heart Association class IV refractory heart failure, patients were randomized to receive T. arjuna bark 500 mg 3 times daily or placebo for 2 weeks followed by crossover to the other treatment, with a washout period of 2 weeks. Following this phase (phase 1), patients who showed improvement with T. arjuna continued treatment in an open-label phase study (phase 2) during which they continued to take T. arjuna for 20 to 28 months (average duration, 24 months). In phase 1, patients treated with T. arjuna demonstrated improvements in walking and effort tolerance, weight loss, and reduction in heart size. Following phase 2, patients receiving T. arjuna showed continued benefit related to ejection fraction and quality of life.(Bharani 1995, Maulik 2012)

In a case-control study, an ethanolic bark extract of T. arjuna inhibited platelet aggregation in controls and in patients with coronary artery disease. Additionally, it was found to attenuate calcium release and P-selectin expression.(Malik 2009)

A case report describes a 50-year-old man with beta-thalassemia minor, hyperlipoproteinemia(a), and hypertension, with an elevated lipoprotein(a) level of 51.8 mg/dL. After 6 months of taking T. arjuna bark stem powder 500 mg 3 times daily, the patient's lipoprotein(a) level dropped to 39 mg/dL.(Dwivedi 2007, Dwivedi 2009)

Dermatologic effects

Clinical data

In a study comparing a water-in-oil emulsion of T. chebula versus its vehicle (control) applied topically to the cheeks of volunteers, T. chebula increased skin moisture content following application. The effect was insignificant regarding time while significant, with respect to base (vehicle) and formulation. Erythema was also reduced with the active formulation. However, effects on skin melanin and sebum were not clinically important.(Akhtar 2012)

Diabetes mellitus

Animal and in vitro data

Chebulagic acid, isolated from T. chebula, was found to exert noncompetitive and reversible inhibition of maltase, suggesting a potential role in the management of diabetes via alpha-glucosidase inhibition.(Gao 2008) In another study, T. chebula fruit extract demonstrated inhibition against alpha-glucosidase, with the ethyl acetate extract exerting the strongest inhibition, likely because of the high content of chebulagic and chebulinic acids.(Sasidharan 2012) Additionally, chebulagic acid 100 mg/kg orally decreased postprandial blood glucose levels in Sprague-Dawley rats receiving maltose (127±6 mg/dL) compared with controls (165±8 mg/dL). However, this effect was not noted in rats receiving sucrose or glucose loads.(Huang 2012)

In mice with streptozotocin-induced diabetes, daily oral administration of an aqueous extract of T. chebula for 2 months decreased blood glucose level by 43% (P<0.01) and significantly reduced HbA1c level compared with baseline.(Murali 2007)

In a study evaluating antidiabetic potential of common traditional herbs, a 50% methanolic extract of T. arjuna was found to inhibit amylase activity.(Saha 2012)

GI effects

Animal data

In a study of morphine-treated rats, an aqueous extract of T. chebula seeds at dosages of 125 mg/kg and 250 mg/kg produced a similar number of fecal pellets as in rats given saline.(Mard 2011)

T. arjuna at doses of 400 mg/kg and 500 mg/kg exerted gastroprotective effects against diclofenac sodium–induced ulceration in a murine model. Specifically, rats receiving T. arjuna showed a reduction in lesion index compared with controls.(Devi 2007) In a similar study, T. arjuna at doses of 100 mg/kg, 400 mg/kg, and 200 mg/kg was gastroprotective (ie, antiulcer and ulcer-healing activity) against 80% ethanol–, diclofenac sodium–, and dexamethasone-induced ulceration, respectively.(Devi 2007, Devi 2007)

Clinical data

A study examining treatment with T. chebula 250 mg capsules orally 4 times per day in patients with hemorrhoids noted improvement in several symptoms, such as pain and hemorrhoid mass, over 4 weeks of treatment.(Andarkhor 2019)

Hepatoprotective effects

Animal data

In animal experiments, T. bellirica(Anand 1997) and T. arjuna(Manna 2006) exhibited hepatoprotective effects. In Swiss albino mice exposed to carbon tetrachloride, aqueous T. arjuna extract protected against alterations in glutathione S-transferase, superoxide dismutase, and catalase levels, suggesting antioxidant defense activities.(Manna 2007)

Clinical data

In a placebo-controlled study in 36 cirrhotic patients, a combination herbal product containing T. arjuna demonstrated a hepatoprotective effect, possibly attributed to diuretic, anti-inflammatory, antioxidant, and immunomodulating properties of the various herbs.(Huseini 2005)

Kidney disease

Clinical data

A T. bellerica extract has demonstrated significant activity in lowering serum uric acid and creatinine levels and increasing estimated glomerular filtration rate in patients with chronic kidney disease.(Pingali 2020)

Periodontal disease

In vitro data

In an in vitro model, ethanolic extracts of T. chebula suppressed growth of oral bacteria and decreased inflammatory cytokine and protease expression. Additionally, osteoclast formation was inhibited. Results suggest T. chebula may play a role in inflammation and bone resorption caused by dental plaque bacteria.(Lee 2017)

Urolithiasis

In vitro data

T. chebula prevented injury against calcium oxalate–induced damage in both NRK-52E and MDCK renal epithelial cells in a dose-dependent manner, suggesting a potential role against urolithiasis.(Tayal 2012) Similarly, T. arjuna inhibited calcium oxalate crystallization in an in vitro model.(Mittal 2015)

Dosing

T. arjuna bark extract 500 mg every 8 hours (reported treatment durations, 1 to 2 weeks) has been used in clinical studies evaluating effects on cardiovascular disorders.(Bharani 2002, Bharani 2004, Dwivedi 2005, Dwivedi 2007, Maulik 2012) Dosages of other Terminalia species have not been clinically defined.

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. One source cautions against taking T. bellirica and T. chebula during pregnancy.(Chevallier 1996)

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.(Sumitra 2001)

Adverse Reactions

Evidence suggests extracts of T. arjuna are well tolerated. Adverse reactions similar to those with placebo (constipation, headache, abdominal discomfort, body ache) were described in 1 clinical trial,(Bharani 2002) while mild gastritis was noted in another.(Dwivedi 2005) In a study of rats, it was suggested that high amounts of T. arjuna extract could cause hepatotoxicity and hypothyroidism.(Parmar 2006)

Information regarding other Terminalia species is limited.

Toxicology

No toxicities occurred when T. arjuna was given to mice at a dose of 2,000 mg/kg.(Subramaniam 2011)

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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