Terminalia arjuna

Arjuna

Traditional usage

The bark, leaves and fruits of arjuna have traditionally been used for urinary discharge, strangury (painful passage of small quantities of urine), leucoderma (white patches on the skin), anaemia, sweating, asthma and tumours. The use of the bark powder for cardioprotection was described over 1200 years ago. It is traditionally prepared as an alcoholic decoction and given along with clarified butter or boiled milk for chest pain. Arjuna is also used traditionally in the treatment of red and swollen mouth, tongue and gums, dysentery, skin eruptions, menstrual disorders, pains and leucorrhoea.

Actions

Antioxidant, cardio-protective, heart tonic, hypotensive, hypolipidaemic, anti-inflammatory, cytoprotective, antiulcer, anticancer, apoptosis inducing, antidiabetic, antibacterial, antiviral, vulnerary.

Energetics: The Taste (Rasa) is astringent and bitter), the Energy (Virya) is cooling with the post-digestive effect (Vipaka) is pungent, the Quality (Guna) is light and dry, the target tissue (Dhatu) is blood, bone and reproductive, the Channels (Srotas) are circulatory and reproductive. It affects all Dosa and purifies excess pitta from the blood.

Indications

  • Arjuna is indicated in chronic cardio-vascular diseases including chronic, stable angina, mild congestive heart failure, weakness of the heart, hypercholesterolemia, hypertension and metabolic syndrome.
  • Adjuvant during chemotherapy
  • Antioxidant therapy in diabetes
  • Gastric ulceration
  • Difficulty in urination
  • General detoxification
  • Externally arjuna is used to improve wound healing.

Contraindications and cautions

Traditionally contraindicated during pregnancy.

Drug interaction

Arjuna has been used concurrently with statins with good results. Information about interactions with beta-blockers or long term statin therapy is lacking.1

Administration and dosage

Arjuna has been used in the dose of 1-2 g/day in various clinical studies. This has been found to be the optimum dose in patients with coronary artery disease. At this dosage, it was well tolerated and produced only minor adverse reactions such as mild gastritis, headache and constipation. No haematological, metabolic, renal or hepatotoxicity has been reported even for long term administration of 24 months.

Dried bark

1-6 g

Liquid extract 1:1 in 45% ethanol

0.7 to 2.0 ml 3 times daily

Description

Arjuna is a 20-30 m deciduous tree of the Combretaceae family. It is found in abundance throughout the mountainous area of North India. It is also found in the forests of Sri Lanka, Burma and Mauritius. Remarkably the tree is pest and disease free. It has huge, often buttressed trunk and horizontally spreading branches. The bark is smooth, pinkish-grey from outside and flakes off in large, curved and rather flat pieces. The size of each piece may vary up to 15 cm or more in length, 10 cm in width and 3-10 mm in thickness. The bark has been used in Ayurvedic medicine for over three centuries, primarily as a cardiac tonic.1

Improvement of cardiac muscle function and subsequent improved pumping activity of the heart seems to be the primary benefit of arjuna. It is thought the saponin glycosides might be responsible for inotropic effects of arjuna, while the flavonoids and OPCs provide free radical antioxidant activity and vascular strengthening.2

Constituents

Arjuna contains triterpenoids including arjunin, arjunic acid, arjunolic acid, arjungenin, and terminic acid. The bark also contains glycosides, including arjunetin, arjunoside I, arjunoside II, arjunaphthanoloside and terminoside A; sitosterol; flavonoids including arjunolone, arjunone, bicalein, luteolin, gallic acid, ethyl gallate, quercetin, kempferol, pelorgonidin, oligomeric and proanthocyanidins; tannis and minerals.1

Therapeutic activities

Cardio-vascular activities

Ancient Indian physicians used the powdered tree bark for alleviating hritshool (angina) and other cardiovascular conditions. Its stem bark possesses glycosides, large quantities of flavonoids, tannins and minerals. Flavonoids have been detected to exert antioxidant, anti-inflammatory and lipid lowering effects while glycosides are cardiotonic. Experimental studies have revealed that the bark exerts significant inotropic and hypotensive effect, increasing coronary artery flow and protecting myocardium against ischemic damage. It has also been detected to have mild diuretic, antithrombotic, prostaglandin E2 enhancing and hypolipidaemic activity. There is clinical evidence of its beneficial effect in coronary artery disease alone or combined with statins.1

Cardio-protective activities

Reactive oxygen species (ROS) including superoxide anion, hydrogen peroxide, hydroxyl radicals, nitric oxide and peroxynitrite have the potential to initiate degenerative processes in human body. The body is protected from oxidative stress induced by ROS by efficient defence systems; however, the capacity of the defensive system is affected by age, diet and health status of the individual. To help keeping proper equilibrium between ROS and defence system components, there is a need to provide antioxidants as part of the diet. There is also a growing body of evidence suggesting that antioxidants contribute to cardioprotection. Nine key plants in Ayurvedic formulations used in the therapy of cardiovascular diseases have been investigated to determine whether antioxidant activity is one of the mechanisms by which these plants exert cardioprotection. However, only arjuna could be demonstrated to have significant antioxidant effect (reduction in cardiac lipidperoxidation).3 Clearly there are many ways plants may exert cardioprotective effects. However, chronic and acute overproduction of reactive oxygen species (ROS) plays a significant role in the development of cardiovascular diseases. The cardioprotective effects of arjuna are partly related to its antioxidant activities and several studies have shown arjuna to protect the heart against myocardial ischemic reperfusion injury.4-6

The crude bark of arjuna has been shown to augments endogenous antioxidant compounds in the rat heart and also prevent oxidative stress associated with ischemic-reperfusion injury of the heart. Dried pulverised bark of arjuna was administered orally to Wistar albino rats in two doses (500 and 750 mg/kg) 6 days per week for 12 weeks. The rat hearts were then subjected to in vitro ischemic-reperfusion injury and it was shown that arjuna (500 mg/kg) raised the levels of endogenous antioxidants (superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT)) and significantly protected the hearts against oxidative stress.4 Oral administration of arjuna for 12 weeks in rabbits confirmed that arjuna augments myocardial antioxidants; SOD, catalase and glutathione along with induction of heat shock proteins. Arjuna has furthermore been shown to prevent oxidative stress, cardiac tissue injury and haemodynamic disturbance induced by ischemic-reperfusion injury in rabbits. The study suggests that arjuna may be beneficial in the treatment of ischemic heart disease.6

A combination of equal proportions of extracts of arjuna, Inula racemosa and Commiphora mukul was administered orally daily for 6 days a week for 60 days in rats. The rats were subsequently subjected to isoproterenol-induced myocardial necrosis. Although the combination did not show statistically significant reduction in myocardial damage, the loss of myocardial high energy phosphates stores and accumulation of lactate were significantly prevented suggesting some benefits may be gained from such a formulation in the prevention of ischemic heart disease.7 Another study found that arjunolic acid did provide significant cardiac protection in isoproterenol-induced myocardial necrosis in rats. Arjunolic acid (15 mg/kg i.p.) has furthermore been shown to prevent the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, alpha-tocopherol, reduced glutathione (GSH), ascorbic acid, lipid peroxide, myeloperoxidase in experimental myocardial necrosis in rats and to restore the electrocardiographic changes towards normalcy.8

More recently arjuna has been shown to also reduce carbon tetrachloride-induced cardiac oxidative stress in mice. Arjuna significantly restored the activities of all antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST)) as well as increased the level of GSH and decreased the level of lipid peroxidation end products. In addition, Ferric Reducing Ability of Plasma (FRAP) assay showed that arjuna enhanced the cardiac intracellular antioxidant activity. Histological studies also supported the cardioprotective role of arjuna.9

The oleanane triterpenes arjunic acid, arjungenin and their glucosides, arjunetin and arjunglucoside II, as well as casuarinin have been identified in several studies to exert significant antioxidant activities and terminoside A has been shown to inhibit nitric oxide production in murine macrophages.10-12

Recently it has been suggested that the cardio-protective role of arjuna bark extract is mediated through alterations in thyroid hormones. Supplementation with L-thyroxine was found to increase the level of thyroid hormone and increase both cardiac and hepatic lipid peroxidation. Co-administration with arjuna extract (21.42 and 42.84 mg/kg) decreased the level of thyroid hormones and also cardiac lipid peroxidation, suggesting a possible mediation of the drug action through an inhibition in thyroid function. These effects were comparable to a standard antithyroid drug, propylthiouracil. When arjuna was administered to animals with normal thyroid function (euthyroid) animals, serum concentrations of thyroid hormones were decreased, whereas the hepatic lipid peroxidation increased indicating a drug-induced toxicity in euthyroid subjects. While low doses of arjuna was found to be non-toxic to the liver, high doses are needed to affect thyroid functions and to prevent cardiac lipid peroxidation.8 The clinical relevance of these studies is unclear.

Hypotensive

An early study found that intravenous injections of arjuna extract induced a dose dependent decrease in blood pressure and heart rate in vivo. The injections also inhibited carotid occlusion response, without affecting the pressor responses, induced by intravenous injection of norepinephrine and by electrical stimulation of preganglionic fibres of the abdominal splanchnic nerve. Hypotension and bradycardia were also observed following the injection of the extract into the lateral cerebral ventricle and vertebral artery. The results of the this study suggest that the hypotensive and bradycardiac effects of arjuna are mainly of central origin.13 However a more recent study suggests that a 70% alcoholic extract exerts hypotensive effects via peripheral mechanisms. Intravenous administration of arjuna was shown to produce dose-dependent hypotension in anaesthetised dogs. The hypotension produced by 6 mg/kg dose of the extract was blocked by propranolol but not by atropine or mepyramine maleate. This indicates that muscarinic or histaminergic mechanisms are not likely to be involved in the hypotension produced by the extract. The blockade by propranolol of the hypotension produced by arjuna indicates that the extract might contain active compounds possessing adrenergic beta2-receptor agonist action and/or that act directly on the heart muscle. The extract did not adversely affect biochemical tests of liver and renal function and haematological parameters.14

Hypolipodaemic

A 50% ethanol extract of arjuna has been shown in a small in vivo study to significantly lower total and LDL cholesterol and improve the LDL to HDL ratio in diet-induced hyperlipidaemic rabbits.15

Group total cholesterol mg/dl
>(p < 0.01)
LDL cholesterol mg/dl
(p < 0.01)
HDL cholesterol mg/dl
(p = n.s.)
triglyceride mg/dl
(p = n.s.)
cholesterol/HDL ratio
(p= n.s.)
LDL/HDL ratio
(p < 0.01).
A Control 574 +/- 61 493 +/- 57 59 +/- 7 108 +/- 13 10.1 +/- 1.3 8.7 +/- 1.3
B (n = 6)
100 mg/kg
320 +/- 29 271 +/- 30 36 +/- 3 67 +/- 6 9.2 +/- 1.1 7.8 +/- 1.1
C (n = 6)
500 mg/kg
217 +/- 44 162 +/- 44 35 +/- 4 101 +/- 26 6.1 +/- 1.0 4.5 +/- 1.0

Arjuna has also been shown to reduce lower lipids and development of atheroma in rabbits on a high cholesterol diet.16

An Ayurvedic formulation containing methanolic extracts of selected parts of plants, Commiphora mukul, Allium sativum, Plumbago indica, Semecarpus anacardium, Hemidesmus indicus, Terminalia arjuna, Tinospora cordifolia, Withania somnifera and Ocimum sanctum was found to scavenge superoxide and hydroxyl radicals in vitro and significantly (p < 0.001) inhibit lipid peroxidation, delay plasma recalcification and enhance the release of lipoprotein lipase enzyme in vivo. The formulation also inhibited chemically-induced platelet aggregation in vitro, which was comparable to heparin. The anti-inflammatory action of the formulation was significant (p < 0.001) with acute and chronic inflammations induced by carrageenan and formalin respectively in rats. The formulation furthermore significantly reduced blood lipids (p < 0.001) and improved HDL in diet-induced hyperlipidaemia in rats over a 30 day period.17

Anti-inflammatory activity

Nitrous oxide activates NFkB, an important transcription factor involved in the body's response to inflammation. The triterpene Terminoside A (isolated from the acetone fraction of the ethanolic extract of stem bark of arjuna) has been shown to potently inhibit nitric oxide production and decreased inducible nitric oxide synthase levels in lipopolysaccharide-stimulated macrophages.18

Gastric ulceration

The anti-oxidant and cytoprotective activities of arjuna are thought to be responsible for its protective effect against gastric ulceration. In vivo studies have shown arjuna to protect the gastric mucosa against diclofenac sodium- or lipopolyssacharide-induced gastric ulceration in rats. The gastroprotective effect of arjuna is probably related to its ability to maintain the membrane integrity by its antilipid peroxidative activity that protects the gastric mucosa against oxidative damage and its ability to strengthen the mucosal barrier, the first line of defence against exogenous and endogenous ulcerogenic agents. A significant increase was observed in pH, non-protein sulfhydryls, reduced glutathione, antioxidants, protein bound carbohydrate complexes, adherent mucus content, nucleic acids with a significant decrease in volume of gastric juice, free and total acidity, pepsin concentration, acid output, lipid peroxide levels and myeloperoxidase activities in arjuna treated animals compared to controls.19-21

Anticancer activities

Antioxidant and down-regulation of anaerobic metabolism

A wide array of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial antimutagenic and anticarcinogenic activities. Various fractions and ellagic acid isolated from arjuna have been shown to have antimutagenic properties in vitro.22-25 the triterpenoid saponin, arjunolic acid, has also been shown to ameliorate arsenic-induced cyto-toxicity in hepatocytes26 and arsenic-induced testicular oxidative stress.27 Arsenic-induced tissue damage is a major concern to the human health. An impaired antioxidant defence mechanism followed by oxidative stress is the major cause of arsenic-induced toxicity, which can lead to reproductive failure. A recent study examined the preventive role of arjunolic acid against arsenic-induced testicular damage in mice. Administration of arsenic (in the form of sodium arsenite, NaAsO2, at a dose of 10 mg/kg body weight) for 2 days significantly decreased the intracellular antioxidant power, the activities of the antioxidant enzymes, as well as the levels of cellular metabolites. In addition, arsenic intoxication enhanced testicular arsenic content, lipid peroxidation, protein carbonylation and the level of glutathione disulfide (GSSG). Exposure to arsenic also caused significant degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. Pre-treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days could prevent the arsenic-induced testicular oxidative stress and injury to the histological structures of the testes. Arjunolic acid had free radical scavenging activity in a cell-free system and antioxidant power in vivo. In summary, the results suggest that the chemo preventive role of arjunolic acid against arsenic-induced testicular toxicity may be due to its intrinsic antioxidant property.27 The aqueous extract of the bark of arjuna has also been shown to protect the liver and kidney tissues against carbon tetrachloride-induced oxidative stress probably by increasing antioxidative defence activities.28

Arjuna may also have important anti-carcinogenic activities by reducing oxidative stress along with inhibition of anaerobic metabolism, both of which are strong features of cancer. Constant production of reactive oxygen species (ROS) during aerobic metabolism is balanced by antioxidant defence system of an organism. Although low level of ROS is important for various physiological functions, its accumulation has been implicated in the pathogenesis of age-related diseases such as cancer and coronary heart disease and neurodegenerative disorders such as Alzheimer's disease. It is generally assumed that frequent consumption of phytochemicals derived from vegetables, fruits, tea and herbs may contribute to shift the balance towards an adequate antioxidant status. Arjuna extract has been shown to increase levels of lipid peroxides associated with nitrosamine-induced liver cancer in rats.29 The antioxidants catalase, superoxide dismutase and glutathione S transferase are low in lymphoma-bearing mice indicating impaired antioxidant defence system. Oral administration of aqueous extract of arjuna has been shown to significantly increase the activities of catalase, superoxide dismutase and glutathione S transferase. Arjuna was furthermore found to down-regulate anaerobic metabolism by inhibiting the activity of lactate dehydrogenase in lymphoma-bearing mice, which was elevated in untreated cancerous mice.30 Cancer cells favour cytoplasmic glycolysis over oxidative phosphorylation in the mitochondria which may confer apoptosis resistance. In a study of rats with N-nitrosodiethylamine-induced hepatocellular carcinoma, the plasma and liver glycolytic enzymes including hexokinase, phosphoglucoisomerase and aldolase were significantly increased while the glyconeogenic enzyme was greatly reduced. These enzymes were significantly reverted to near normal range after oral administration of arjuna for 28 days. The modulation of the enzymes constitute the depletion of energy metabolism leads to inhibition of cancer growth.29

Adjuvant chemotherapy

Arjuna may also play role during chemotherapy. The butanolic fraction of arjuna bark extracts has been shown to reduce doxorubicin-induced cardiotoxicity in vivo. The arjuna extract was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and arjuna-treated controls were administered 20 mg/kg doxorubicin intraperitonially. There was a significant decrease in myocardial superoxide dismutase and reduced glutathione in animals treated with doxorubicin. Co-treatment of arjuna and doxorubicin resulted in an increase in the cardiac antioxidant enzymes, decrease in serum serum creatine kinase-MB (CKMB) levels and reduction in lipid peroxidation as compared to doxorubicin-treated animals. Histological examinations confirmed the protective effects.31

Anti-proliferation and apoptosis

Gallic acid, ethyl gallate, and especially the flavone luteolin from arjuna have been shown to inhibit cancer cell growth in vitro32 and both the acetone and methanol extracts of arjuna have been shown to inhibit the growth of human normal fibroblasts, osteosarcoma, and glioblastoma cells in vitro. The results suggest that arjuna induces growth arrest of transformed cells by p53-dependent and as well as p53-independent pathways.33 Casuarinin has also been shown to induce apoptosis (programmed cell death) and cell cycle arrest in human breast adenocarcinoma cells.34 Arjunic acid, arjungenin, arjunetin and arjunoglucoside I have been identified as being cytotoxic against oral, ovarian and liver cancer cell lines.35 Arjuna has also been shown to inhibit the proliferation of human hepatoma cells by inducing apoptosis in vitro. Depletion of glutathione in the hepatoma cells may be involved in the induction of apoptosis of the cancer cells.36

Antidiabetic

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. High doses of arjuna ethanolic extract (250 and 500 mg/kg body weight) has been shown to produce significant (p<0.05) reduction in lipid peroxidation in alloxan-induced diabetic rats. The extract also causes a significant (p<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups and non protein sulfhydryl groups in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of arjuna bark. The result indicates that the extract exhibits the antioxidant activity through correction of oxidative stress which supports the traditional use of arjuna in diabetes.37

Anti-microbial

Of 34 plants, selected on the basis of folklore medicinal reports practised by the tribal people of Western Ghats, India, Cassia fistula, Terminalia arjuna and Vitex negundo showed significant antibacterial activity against Escherichia coli, Klebsiella aerogenes, Proteus vulgaris, and Pseudomonas aerogenes (gram-negative bacteria)38 and casuarinin has been shown to have antiviral activity against herpes simplex type 2 in vitro. The hydrolysable tannin inhibited viral attachment and penetration.39 The estimated increase in hydroxyproline content of the granulation tissue of the excision wounds indicated rapid collagen turnover thus, leading to rapid healing of the wounds.

Wound healing

Externally, arjuna can be used in wound healing. The tannin fraction of arjuna has been shown to increase the tensile strength of an incision wound in vivo and improve epithelialization compared with controls (p < 0.05). The fraction was also shown to be antibacterial against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes but not Candida albicans. The astringent effect of tannins draws the tissues closer together.40 Another study compared the wound healing effects of the tannins with a 50% ethanolic extract of the bark in incision and excision wound models, after oral or topical application in form of a hydrogel. The findings revealed a statistically significant increase in the tensile strength of the incision wounds and increase in the percent reduction in wound size of excision wounds as compared to control. However, the topical treatment with tannins was found to be superior in both incision and excision wound studies. The estimated increase in hydroxyproline content of the granulation tissue of the excision wounds indicated rapid collagen turnover, thus leading to rapid healing of the wounds.41 The wound healing effect of arjuna is comparable to that of the standard drug nitrofurazone in terms of wound contracting ability, epithelization period, tensile strength and regeneration of tissues at the wound area.

Clinical studies

Cardiomyopathy

The results of a small study suggest that arjuna may be a beneficial adjunctive therapy in cardiomyopathy. Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received arjuna bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvant to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of arjuna and placebo therapy and results were compared. Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular end diastolic (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and end systolic volume (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P < 0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs. 30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life.

Angina

A small study found arjuna beneficial in angina pectoris and congestive heart failure. Bark stem powder of arjuna, 500 mg 8 hourly, was administered to 10 patients of postmyocardial infarction angina and two patients of ischaemic cardiomyopathy, in a dose of 500 mg 8 hourly postoperatively, for a period of three months. The patients were also on conventional treatment comprising of nitrates, aspirin and/or calcium channel blockers. Twelve age, sex, body mass index and ECG-matched patients of postmyocardial infarction angina receiving only conventional treatment served as controls. Significant reduction in anginal frequency was noted in both groups (3.5 +/- 1.98 to 1.08 + 1.08 per day vs 3.10 + 0.72 to 1.17 + 0.84 per day). However, only the arjuna treated patients showed significant improvement in left ventricular ejection fraction (42.25 + 9.96 to 52.67 + 12.32% vs 51.83 + 5.99 to 49.83 + 2.52%) and reduction in left ventricular mass (159.18 + 51.11 to 127.47 + 52.40 gm/m2 vs 159.11 + 38.92 to 160.78 + 54.23 gm/m2) on echocardiography following three months of therapy. Both patients with ischaemic cardiomyopathy showed significant symptomatic relief in coronary heart failure from NYHA class III to NYHA class I. Prolonged administration of arjuna did not show any adverse effects on renal, hepatic and haematological parameters.42

The results of another small suggest that monotherapy with arjuna is fairly effective in patients with symptoms of stable angina pectoris. However, it has a limited role in unstable angina. The effect of bark powder of arjuna on anginal frequency, blood pressure, body mass index, blood sugar, cholesterol and HDL-cholesterol was studied in 15 stable (Group A) and 5 unstable (Group B) angina patients before and 3 months after arjuna therapy. Tread mill test (TMT) and echocardiographic left ventricular ejection fraction was evaluated in some cases. There was 50% reduction in anginal episodes in the stable angina group (P < 0.01). Tread mill test performance improved from moderate to mild changes in 5 patients and one with mild changes became negative for ischemia. The time to the onset of angina and appearance of ST-T changes on TMT after T. arjuna was delayed significantly. However, in patients with unstable angina there was an insignificant reduction in anginal frequency. These patients also needed diltiazem, B-blockers and nitroglycerine in addition to arjuna. The drug lowered systolic blood pressure and body mass index to a significant level (p < 0.05) and increased HDL-cholesterol only slightly along with marginal improvement in left ventricular ejection fraction in stable angina patients. There were no deleterious effects on liver or kidney functions.43

The beneficial effects of arjuna on stable angina was confirmed in another pilot study. Ten patients with stable angina pectoris were given arjuna extract (brand Hartone) 2 capsules twice daily for 6 weeks and 1 capsule twice daily for the next 6 weeks. Efficacy was assessed by considering the reduction in the number of anginal episodes and improvement in stress test. The results were compared with 10 patients of stable angina pectoris on isosorbide mononitrate (Imdur, Duride) 20 mg twice daily. Arjuna provided symptomatic relief in 80% of patients and isosorbide mononitrate in 70%. Although patients of both groups showed improvement in several stress test parameters compared to base line, the difference was not statistically significant. Arjuna improved blood pressure response to stress test in two patients and ejection fraction in one. Arjuna was better tolerated than isosorbide mononitrate and showed no evidence of hepatic or renal impairment.44

In a larger study arjuna bark extract (500 mg) was found be comparable with isosorbide mononitrate (40 mg/day) (Imdur, Duride) in improving clinical and treadmill exercise test parameters in men with stable angina. Fifty-eight males with chronic stable angina (NYHA class II-III) with evidence of provocable ischemia on treadmill exercise test received arjuna (500 mg 8 hourly), isosorbide mononitrate (40 mg/daily) or a matching placebo for one week each, separated by a wash-out period of at least three days in a randomised, double-blind, crossover design. They underwent clinical, biochemical and treadmill exercise evaluation at the end of each therapy which were compared during the three therapy periods. Arjuna therapy was associated with significant decrease in the frequency of angina and need for isosorbide dinitrate (5.69+/-6.91 mg/week v. 18.22+/-9.29 mg/week during placebo therapy, p<0.005). The treadmill exercise test parameters improved significantly during therapy with Terminalia arjuna compared to those with placebo. The total duration of exercise increased (6.14+/-2.51 min v. 4.76+/-2.38 min, p<0.005), maximal ST depression during the longest equivalent stages of submaximal exercise decreased (1.41+/-0.55 mm v. 2.21+/-0.56 mm, p<0.005), time to recovery decreased (6.49+/-2.37 min v. 9.27+/-3.39 min, p<0.005) and higher double products were achieved (25.75+/-4.81x10(3) v. 23.11+/-4.83x10(3), p<0.005) during arjuna therapy. Similar improvements in clinical and treadmill exercise test parameters were observed with isosorbide mononitrate compared to placebo therapy. No significant differences were observed in clinical or treadmill exercise test parameters when arjuna and isosorbide mononitrate therapies were compared. No significant untoward effects were reported during Terminalia arjuna therapy.45

Arjuna may also be beneficial in ischaemic mitral regurgitation. In a study of 40 patients suffering ischemic mitral regurgitation following acute myocardial infarction, 500 mg arjuna significantly decreased the mitral regurgitation, improved E/A ratio (a sign of diastolic dysfunction) and reduced angina frequency compared to placebo after three months therapy.46

Hypercholesterolaemia

Arjuna tree bark powder has significant antioxidant action that is comparable to vitamin E. In addition, it also has a significant hypocholesterolaemic effect. In a study, one hundred and five patients with coronary heart disease (CHD) were divided into 3 groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. Group I received placebo capsules; Group II vitamin E capsules 400 units/day; and Group III received finely pulverised arjuna tree bark-powder (500 mg) in capsules daily. Response rate in various groups varied from 86% to 91%. Neither Vitamin E nor placebo caused any significant changes in total, HDL, LDL cholesterol and triglycerides levels (paired t-test p > 0.05). In the arjuna treated group, however, there was a significant decrease in total cholesterol (-9.7 +/- 12.7%), and LDL cholesterol (-15.8 +/- 25.6%) (paired t-test p < 0.01). Vitamin E and arjuna both decreased lipid peroxide levels significantly (p < 0.01).47

Dwivedi reports that a study described in a thesis by S. Khalil in 2005 found that arjuna bark powder along with statin for 3 months resulted in 15% decrease in total cholesterol, 11% in triglycerides and 16% in LDL-cholesterol. There was minimal decline in lipoprotein and nitrite levels. The results suggest that arjuna may work synergistically with statin in hyperlipidaemia.1

Metabolic syndrome

A case study of a patient suffering metabolic syndrome suggests that arjuna may be beneficial in metabolic syndrome. In addition, this patient also exhibited beta-thalassemia minor and hyperlipoproteinemia. Lipoprotein levels diminished significantly (24.71% ) following therapy with bark-stem powder of arjuna.48

Liver cirrhosis

Liv-52 is a well known Ayurvedic formulation containing arjuna which has been shown to be beneficial in chronic liver disease. Liv-52 additionally contains mandur basma (a special Ayurvedic preparation of iron), Tamarix gallica and herbal extracts of Capparis spinosa, Cichorium intybus, Solanum nigrum, and Achillea millefolium. Liv-52 was compared to placebo in 36 cirrhotic patients. Patients treated with Liv-52 for 6 months had significantly better child-pugh score (used to assess the prognosis of chronic liver disease), decreased ascites and decreased serum ALT and AST compared to placebo. The results suggest that Liv-52 has hepatoprotective effect in cirrhotic patients and that the protective effect can be attributed to diuretic, anti-inflammatory, anti-oxidative, and immunomodulating properties of the component herbs.49

Smoking

Smoking, largely through increased oxidative stress, causes endothelial dysfunction which is an early key event in atherosclerosis. Although controversial, smoking cessation and antioxidant vitamin therapy are shown to have beneficial role by restoring altered endothelial physiology. Smokers have impaired endothelium-dependent but normal endothelium-independent vasodilation as determined by brachial artery reactivity studies. A small study has found that arjuna therapy for two weeks leads to significant regression in endothelial abnormality in smokers compared to matched controls.50

Reference List

  1. Dwivedi S. Terminalia arjuna Wight & Arn.--a useful drug for cardiovascular disorders. J Ethnopharmacol 2007; 114(2):114-129.
  2. Thorne Review. Terminalia arjuna. Altern Med Rev 1999; 4(6):436-437.
  3. TC JM, Seneviratne CK, Thabrew MI, Abeysekera AM. Antiradical and antilipoperoxidative effects of some plant extracts used by Sri Lankan traditional medical practitioners for cardioprotection. Phytother Res 2001; 15(6):519-523.
  4. Gauthaman K, Maulik M, Kumari R, Manchanda SC, Dinda AK, Maulik SK. Effect of chronic treatment with bark of Terminalia arjuna: a study on the isolated ischemic-reperfused rat heart. J Ethnopharmacol 2001; 75(2-3):197-201.
  5. Karthikeyan K, Bai BR, Gauthaman K, Sathish KS, Devaraj SN. Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury. Life Sci 2003; 73(21):2727-2739.
  6. Gauthaman K, Banerjee SK, Dinda AK, Ghosh CC, Maulik SK. Terminalia arjuna (Roxb.) protects rabbit heart against ischemic-reperfusion injury: role of antioxidant enzymes and heat shock protein. J Ethnopharmacol 2005; 96(3):403-409.
  7. Seth SD, Maulik M, Katiyar CK, Maulik SK. Role of Lipistat in protection against isoproterenol induced myocardial necrosis in rats: a biochemical and histopathological study. Indian J Physiol Pharmacol 1998; 42(1):101-106.
  8. Sumitra M, Manikandan P, Kumar DA, Arutselvan N, Balakrishna K, Manohar BM et al. Experimental myocardial necrosis in rats: role of arjunolic acid on platelet aggregation, coagulation and antioxidant status. Mol Cell Biochem 2001; 224(1-2):135-142.
  9. Manna P, Sinha M, Sil PC. Phytomedicinal activity of Terminalia arjuna against carbon tetrachloride induced cardiac oxidative stress. Pathophysiology 2007; 14(2):71-78.
  10. Pawar RS, Bhutani KK. Effect of oleanane triterpenoids from Terminalia arjuna--a cardioprotective drug on the process of respiratory oxyburst. Phytomedicine 2005; 12(5):391-393.
  11. Sun FY, Chen XP, Wang JH, Qin HL, Yang SR, Du GH. Arjunic acid, a strong free radical scavenger from Terminalia arjuna. Am J Chin Med 2008; 36(1):197-207.
  12. Chen CH, Liu TZ, Kuo TC, Lu FJ, Chen YC, Chang-Chien YW et al. Casuarinin protects cultured MDCK cells from hydrogen peroxide-induced oxidative stress and DNA oxidative damage. Planta Med 2004; 70(11):1022-1026.
  13. Singh N, Kapur KK, Singh SP, Shanker K, Sinha JN, Kohli RP. Mechanism of Cardiovascular Action of Terminalia arjuna. Planta Med 1982; 45(6):102-104.
  14. 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.
  15. Ram A, Lauria P, Gupta R, Kumar P, Sharma VN. Hypocholesterolaemic effects of Terminalia arjuna tree bark. J Ethnopharmacol 1997; 55(3):165-169.
  16. Shaila HP, Udupa SL, Udupa AL. Hypolipidemic activity of three indigenous drugs in experimentally induced atherosclerosis. Int J Cardiol 1998; 67(2):119-124.
  17. Mary NK, Babu BH, Padikkala J. Antiatherogenic effect of Caps HT2, a herbal Ayurvedic medicine formulation. Phytomedicine 2003; 10(6-7):474-482.
  18. Ali A, Kaur G, Hamid H, Abdullah T, Ali M, Niwa M et al. Terminoside A, a new triterpene glycoside from the bark of Terminalia arjuna inhibits nitric oxide production in murine macrophages. J Asian Nat Prod Res 2003; 5(2):137-142.
  19. Devi RS, Kist M, Vani G, Devi CS. Effect of methanolic extract of Terminalia arjuna against Helicobacter pylori 26695 lipopolysaccharide-induced gastric ulcer in rats. J Pharm Pharmacol 2008; 60(4):505-514.
  20. Devi RS, Narayan S, Vani G, Srinivasan P, Mohan KV, Sabitha KE et al. Ulcer protective effect of Terminalia arjuna on gastric mucosal defensive mechanism in experimental rats. Phytother Res 2007; 21(8):762-767.
  21. Devi RS, Narayan S, Vani G, Shyamala Devi CS. Gastroprotective effect of Terminalia arjuna bark on diclofenac sodium induced gastric ulcer. Chem Biol Interact 2007; 167(1):71-83.
  22. Kaur S, Grover IS, Kumar S. Antimutagenic potential of ellagic acid isolated from Terminalia arjuna. Indian J Exp Biol 1997; 35(5):478-482.
  23. Kaur K, Arora S, Kumar S, Nagpal A. Antimutagenic activities of acetone and methanol fractions of Terminalia arjuna. Food Chem Toxicol 2002; 40(10):1475-1482.
  24. Kaur K, Arora S, Kumar S, Nagpal A. Modulatory effect of phenolic fractions of Terminalia arjuna on the mutagenicity in Ames assay. J Environ Pathol Toxicol Oncol 2002; 21(1):45-56.
  25. Pasquini R, Scassellati-Sforzolini G, Villarini M, Moretti M, Marcarelli M, Fatigoni C et al. In vitro protective effects of Terminalia arjuna bark extracts against the 4-nitroquinoline-N-oxide genotoxicity. J Environ Pathol Toxicol Oncol 2002; 21(1):33-44.
  26. Manna P, Sinha M, Pal P, Sil PC. Arjunolic acid, a triterpenoid saponin, ameliorates arsenic-induced cyto-toxicity in hepatocytes. Chem Biol Interact 2007; 170(3):187-200.
  27. Manna P, Sinha M, Sil PC. Protection of arsenic-induced testicular oxidative stress by arjunolic acid. Redox Rep 2008; 13(2):67-77.
  28. 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.
  29. Sivalokanathan S, Ilayaraja M, Balasubramanian MP. Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. Mol Cell Biochem 2006; 281(1-2):87-93.
  30. Verma N, Vinayak M. Effect of Terminalia arjuna on antioxidant defense system in cancer. Mol Biol Rep 2008.
  31. Singh G, Singh AT, Abraham A, Bhat B, Mukherjee A, Verma R et al. Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity. J Ethnopharmacol 2008; 117(1):123-129.
  32. Pettit GR, Hoard MS, Doubek DL, Schmidt JM, Pettit RK, Tackett LP et al. Antineoplastic agents 338. The cancer cell growth inhibitory. Constituents of Terminalia arjuna (Combretaceae). J Ethnopharmacol 1996; 53(2):57-63.
  33. 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 Anim 2000; 36(8):544-547.
  34. Kuo PL, Hsu YL, Lin TC, Lin LT, Chang JK, Lin CC. Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cells. Planta Med 2005; 71(3):237-243.
  35. Saxena M, Faridi U, Mishra R, Gupta MM, Darokar MP, Srivastava SK et al. Cytotoxic agents from Terminalia arjuna. Planta Med 2007; 73(14):1486-1490.
  36. Sivalokanathan S, Vijayababu MR, Balasubramanian MP. Effects of Terminalia arjuna bark extract on apoptosis of human hepatoma cell line HepG2. World J Gastroenterol 2006; 12(7):1018-1024.
  37. Raghavan B, Kumari SK. Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats. Indian J Physiol Pharmacol 2006; 50(2):133-142.
  38. Perumal SR, Ignacimuthu S, Sen A. Screening of 34 Indian medicinal plants for antibacterial properties. J Ethnopharmacol 1998; 62(2):173-182.
  39. Cheng HY, Lin CC, Lin TC. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral Res 2002; 55(3):447-455.
  40. Chaudhari M, Mengi S. Evaluation of phytoconstituents of Terminalia arjuna for wound healing activity in rats. Phytother Res 2006; 20(9):799-805.
  41. Rane MM, Mengi SA. Comparative effect of oral administration and topical application of alcoholic extract of Terminalia arjuna bark on incision and excision wounds in rats. Fitoterapia 2003; 74(6):553-558.
  42. Dwivedi S, Jauhari R. Beneficial effects of Terminalia arjuna in coronary artery disease. Indian Heart J 1997; 49(5):507-510.
  43. Dwivedi S, Agarwal MP. Antianginal and cardioprotective effects of Terminalia arjuna, an indigenous drug, in coronary artery disease. J Assoc Physicians India 1994; 42(4):287-289.
  44. Kumar PU, Adhikari P, Pereira P, Bhat P. Safety and efficacy of Hartone in stable angina pectoris--an open comparative trial. J Assoc Physicians India 1999; 47(7):685-689.
  45. 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 arjuna with isosorbide mononitrate. Indian Heart J 2002; 54(2):170-175.
  46. Dwivedi S, Aggarwal A, Agarwal MP, Rajpal S. Role of Terminalia arjuna in ischaemic mitral regurgitation. Int J Cardiol 2005; 100(3):507-508.
  47. Gupta R, Singhal S, Goyle A, Sharma VN. Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark powder: a randomised placebo-controlled trial. J Assoc Physicians India 2001; 49:231-235.
  48. Dwivedi S, Kumar V. Beta-thalassemia, hyperlipoproteinemia(a), and metabolic syndrome: its low-cost holistic therapy. J Altern Complement Med 2007; 13(2):287-289.
  49. 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(9):619-624.
  50. Bharani A, Ahirwar LK, Jain N. Terminalia arjuna reverses impaired endothelial function in chronic smokers. Indian Heart J 2004; 56(2):123-128.