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Terminalia arjuna: Phytochemistry, pharmacognosy and pharmacological studies

 

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About Author:
Amol.A.Dambal,
Department of Pharmacognosy and Phytochemistry
Govt. College of pharmacy, Kathora naka,
Amravati-444604. (M.S.), INDIA.

ABSTRACT:
The herbal remedies have been employed in various medical systems for the treatment and management of different diseases. The plant Terminalia arjuna has been used in different system of traditional medication for the treatment of diseases and ailments of human beings. The plants contain Arjunilic acid, Triterpine glycosides like Arjunetosides I, II, III, IV, Arjunine and Arjunetein. The bark is rich in Saponnins, natural anti-oxidants (flavonoids-arjunone,arjunolone,leteilin), gallic acid, ellagic acid , phytosterols, rich in minerals like ca,  mg, zn and co, reducing sugars & coloring matter. It has been reported as Cardio tonic, Hepato-protective, Immunomodulatory, Antihyperglycemic, Antihyperlipidemic, Analgesic and Anti-Inflammatory, Antibacterial and Antiulcer properties.The current study is therefore carried out to provide requisite phytochemical and Pharmacological detail about the plant. The plant is cultivated in different parts of India on a small scale at present However; systematic information on different aspects of this species is not available. In this review, an attempt has been made to present this information.

Reference Id: PHARMATUTOR-ART-1193

INTRODUCTION:
Terminalia arjuna is a large, evergreen tree, with a spreading crown and dropping branches. It’s grown in most parts of India and has been used in Ayurvedic formulation since ancient times. Besides its wide range of medicinal uses, Terminalia arjuna is planted for shades and ornamental purposes. The powder of Arjuna is produced from the grinding and sieving of stem bark. It has following advantages like free of storage, Easy for intake for all ages of life; suitable form for Medicine can be prepared. Terminalia’s active constituents include tannins, cardenolide, triterpenoid saponins (arjunic acid, arjunolic acid, arjungenin, arjun glycosides), flavonoids (arjunone, arjunolone,luteolin), gallic acid, ellagic acid, phytosterols, calcium, magnesium, zinc, and copper.1,2.Improvement of cardiac muscle function and subsequent improved pumping activity of the heart seems to be the primary benefit of Terminalia. It is thought the saponin glycosides might be responsible for the inotropic effect of Terminalia, while the flavonoids provide free radical antioxidant activity and vascular strengthening.3 A dose-dependent decrease in heart rate and blood pressure was noted in dogs given Terminalia intravenously.4 Recently, two new cardenolide cardiac glycosides were isolated from the root and seed of Terminalia.5,6 The main action of these cardenolides is to increase the force of cardiac contraction by means of a rise in both intracellular sodium and calcium.

BOTANICAL DESCRIPTION:
Terminalia arjuna is a deciduous tree found throughout India growing to a height of 60-90feet. The thick, white-to-pinkish-gray bark has been used in India’s native Ayurvedic medicine for over three centuries, primarily as a cardiac tonic. Clinical evaluation of this botanical medicine indicates it can be of benefit in the treatment of coronary artery disease, heart failure, and possibly hypercholesterolemia. It has also been found to be antiviral and antimutagenic.

SCIENTIFIC CLASSIFICATION:

Kingdom:Plantae

Division:Magnoliophyta

Class:Magnoliopsida

Order:Myrtales

Family:Combretaceae

Genus:Terminalia

Species:T. arjuna

MICROSCOPY:
cork consists of few layers of tangentially running and radially elongated cells;phellogen,2to4 celled thick, phelloderm narrow, consisting of 4 to 6 rows of tangentially elongated and radially arranged cells, Phloem, very broad, traversed by uniserriate medullary rays running straight and parallel occasionally becoming slightly curved near the rosette crystal; groups of phloem fibres, lignified, thin-walled, tangentially arranged, associated with idioblasts containing clusters and rossetes of calcium oxalate. Some parenchymatous cells of cortex and secondary phloem contains  reddish brown pigment and some cells contain starch grains.

PHYTOCHEMISTRY: Arjuna contains specific active constituents namely     Arjunilic acid, Tomentosic acid, Sitossterol, Triterpine glycosides like Arjunetosides I, II, III, IV, Arjunine and Arjunetein. The bark is rich in Saponnins, natural anti-oxidants (flavonoids-arjunone,arjunolone,leteilin), gallic acid, ellagic acid,  phytosterols, rich in minerals like calcium, magnesium, zinc and copper, reducing sugars & coloring matter.

PHARMACOLOGY:

ANTHELMINTIC ACTIVITY:
the anthelmintic activity of Terminalia arjuna (Roxb.) bark done by Hafiz Allah  Bachaya. Lethal median concentration (LC50 values) of methanolic extract of T. arjuna bark in egg hatch and Larval development tests against Haemonchus contortus ova and larva were found to be 645.65 and 467.74 μg mL-1, respectively. In adult motility assay, efficacy of the extract was evident by the mortality of H. contortus at different hours post exposure. In vivo results revealed maximum (87.3%) egg count percent reduction (ECR) in sheep treated with crude methanolic extract 3 g kg-1 body weight on day 11 post-treatment (PT). The data revealed dose-dependent anthelmintic activity both in the in vitro and in vivo studies, thus justifying its use in the traditional medicine system of Pakistan.

HEPATO-PROTECTIVE ACTIVITY:
Carbon tetrachloride (CCl4) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl4. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of Ayurvedic formulations, on CCl4 induced oxidative stress and resultant dysfunction in the livers and kidneys of mice.          

Methods: Animals were pretreated with the aqueous extract of TA (50 mg/kg body weight) for one week and then treated with CCl4 (1 ml/kg body weight) in liquid paraffin (1:1, v/v) for 2 days. Serum marker enzymes, namely, glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were estimated in the sera of all study groups. Antioxidant status in both the liver and kidney tissues were estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); as well as by determining the levels of thiobarbutaric acid reactive substances (TBARS) and reduced glutathione (GSH). In addition, free radical scavenging activity of the extract was determined from its DPPH radical quenching ability.

STUDY OF INTERACTION BETWEEN ANTIOBESITY AND HYPOLIPIDEMIC DRUGS:
To study the interaction between antiobesity drug, topiramate, and hypolipidemic drug, atorvastatin, in rats.
Methods: Obesity was induced in Wistar albino rats by administering cafeteria diet (CD) for 40 days and divided into 5 groups. While one group served as control, each other group received either alone or in combination with either topiramate, atorvastatin ortopiramate plus atorvastatin. The animals were treated with the drugs for 7 days. On 7th day, 2 hr after drug administration, the body weight, organ weights, rectal temperature, locomotor activity and various biochemical parameters like serum glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were determined. The data were analyzed statistically.

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ANTIDIABETIC EFFECT:
The present study was carried out to evaluate the antidiabetic effect of T.arjuna stem bark extract and to study the activities of hexokinase, aldolase and phosphogluco isomerase, and gluconeogenic enzymes such as glucose-6-phosphatase and fructose -1,6-diphosphatase in liver and kidney of normal and alloxan induced diabetic rats. Oral administration of ethanolic extract of bark (250 and 500mg/kg body weight) for 30 days, resulted in significant decrease of blood glucose from 302.67 ± 22.35 to 82.50 ± 04.72 and in a decrease in the activities of glucose-6-phosphatase, fructose-1,6-disphosphatase, aldolase and an increase in the activityof phosphoglucoisomerase and hexokinase in tissues. However, in the case of 250 mg / kg body weight of extract, less activity was observed. The study clearly shows that the bark extract of T.arjuna possesses potent antidiabetic activity.

ANTIINFLAMATORY, IMMUNOMODULATORY & ANTINORCICEPTIVE ACTIVITY: 
Terminalia arjuna bark pawder (400mg|kg.po) significantly reduced formalin induced oedema at 24 hr, but not carraginan induced paw oedema. It significantly increased the anti-SRBT antibody titre in secondary phase of immune response. The same dose significantly reduced duration of licks & bites in both phases of formalin induced pain response & showed significant increase in tail flick latency at higher dose (800mg| kg,po). These effect of T. arjuna were antagonized by pretreatment with naloxone (1mg|kg, ip). In another series of experiments, mice pretreated with morphinefor three days in increasing doses (10, 15, 20mg|kg, twice a daily) showed deacreased response in antinorciceptive activity of morphine (5mg|kg, ip). Further cross tolerance is observed with T.arjuna in morphine tolerance animals. These finding support the hypothesis that T.arjuna has antiinflamatory potential against some phlogistic agent along with some immunomodulatory activity & also has antinorciceptive action probably mediated via central opioids receptors.

TERMINALIA ARJUNA A USEFUL DRUG  FOR CARDIOVASCULAR DISORDERS:
Ancient  Indian  physicians  used  the  powdered  tree  bark  of  Terminalia  arjuna Wight  &  Arn.  For alleviating “hritshool” (angina) and other Cardiovascular conditions. Its stem bark possesses glycosides, large quantities of ?avonoids, tannins and minerals. Flavonoids have been detected To exert antioxidant, anti-in?ammatory and lipid lowering effects while glycosides are cardiotonic, thus making Terminalia arjuna unique amongst Currently used medicinal plants. In this review an attempt has been made to discuss various aspects of its ethnomedical, pharmacognostical, Phytochemical, pharmacological and clinical relevance to cardiovascular conditions. Experimental studies have revealed its bark exerting signi?cant Inotropic and hypotensive effect, increasing coronary artery ?ow and protecting myocardium against ischemic damage. It has also been detected To have mild diuretic, antithrombotic, prostaglandin E2 enhancing and hypolipidaemic activity. There is ample clinical evidence of its bene?cial Effect in coronary artery disease alone and along with statin. However, toxicological studies in experimental animals are lacking. Considering Its anti-ischemic activity and its potential to correct dyslipidemia, reduce left ventricular mass and increase left ventricular ejection fraction, it is Essential to examine the molecular mechanism of its action and its core constituents. Proposition to administer Terminalia arjuna along with statins Deserves to be explored in depth for de?ning its place in the over all management and prevention of coronary artery disease.

ANTI-LEISHMANIAL AND ANTI-CANCER ACTIVITIES
Terminalia arjuna Roxb (Combretaceae) is commonly known as Arjjhan and Arjun in Bengal, India. The anti-leishmanial and anticancer activities of a pentacyclic triterpenoid isolated from its leaves were evaluated. Dried and crushed leaves of Terminalia arjuna were de-fatted with petroleum ether (40 - 60°C) and extracted with methanol. The extract was subjected to column chromatography and column fractions were monitored on TLC plates developed in a suitable solvent system. Structures of the isolated pure compounds were elucidated by infra-red spectroscopy, mass spectrometry and nuclear magnetic resonance spectroscopy. One of the compounds was screened for anti-leishmanial activity against promastigotes of Leishmania donovani, and anti-cancer activity on K562 leukaemic cell line.  A pentacyclic triterpenoid, characterized as 3β-hydroxyurs-12-en-28-oic acid (together with ß-D-glucoside) and designated ursolic acid, was successfully isolated. The structure was determined on the basis of spectroscopic analyses. In vitro anti-leishmanial activity against promastigotes of Leishmania donovani (strain AG 83) and anti-cancer activity on K562 leukaemic cell line were shown by the isolated ursolic acid.  The methanol extract of the leaves of Terminalia arjuna led to the isolation of a pentacyclic triterpenoid, ursolic acid. This compound demonstrated in vitro anti-leishmanial and anti-cancer activities.

ANTIALLERGIC AND ANTI-ASTHMATIC ACTIVITIES:
In the present study, the alcoholic extract of Terminalia arjuna (TA) and Arjunolic acid (AA) were studied for its anti-asthmatic and anaphylactic activity. Treatment with TA (250 and 500 mg/kg) and AA (50 and 100 mg/kg) has shown significant protection against mast cell disruption in rats induced by compound 48/80. TA and AA also protected the guinea pig against histamine as well as acetylcholine induced bronchospasm. Both TA and AA exhibited better protection against histamine release against acetylcholine release. Anti-asthmatic activity may be possibly due membrane stabilizing potential and inhibition of antigen induced histamine and acetylcholine release.

ANTIULCER ACTIVITY:
The methanol extract of the bark of Terminalia arjuna (Combretaceae) (TAE) showed marked antiulcer and ulcer healing activity against 80% ethanol (ETH), diclofenac sodium (DIC) and dexamethasone (DEX) induced ulcer models dose dependently at doses of 100, 400 and 200 mg/kg body weight respectively. Gastric mucosal analysis of DEX induced rats were associated with changes in the levels of protein, protein bound carbohydrate complexes, lipid peroxides (LPO), glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) compared with control rats. whereas the activities of GPx remained unaltered in all groups. In DEX + TAE rats, the levels of protein and protein bound carbohydrate complexes were increased when compared with DEX rats. The results indicate that the gastroprotective effect of TAE 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 defense against exogenous and endogenous ulcerogenic agents

CONCLUSION:
Medicinal plants are the local heritage with the global importance. World is endowed with a rich wealth of medicinal plants. Medicinal plants also play an important role in the lives of rural people, particularly in remote parts of developing countries with few health facilities. The present review reveals that Terminalia arjuna is utilized for the treatment of some common disease. In the present review we have congregated information pertaining to botanical, phytochemical, pharmacological studies. The plant has been studied for their various pharmacological activities like antioxidant, antihyperglycemic, antihyperlipidemic, cardio protective, immunomodulatory effects, hepato protective, in hyperthyroidism, hyperglycemia and lipid peroxidation, analgesic and anti-Inflammatory,  anthelmintics , antinorciceptive activity studies have also been studied. Therefore it is necessary to exploit its maximum potential in the field of medicinal and pharmaceutical sciences for novel and fruitful application.

References:
1) Hafiz Allah Bachaya, In Vitro and In Vivo Anthelmintic Activity of Terminalia arjuna Bark International journal of agriculture & biology issn print: 1560–8530; issn online: 1814–9596.
2) Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Warwick, Queensland, Australia. Phyto-therapy Press; 1996:131-133.
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4) Khanna AK, Ramesh C, Kapoor NK. Terminalia arjuna: an Ayurvedic cardiotonic regulates lipid metabo-lism in hyperlipidaemic rats. Phototherapy Res 1996; 10:663-665.
5)    Shridhar Dwivedi, Terminalia arjuna A useful drug for cardiovascular disorders Preventive Cardiology Group, University College of Medical Sciences, University of Delhi, Delhi110095, India.
6)    B. Ragavan* and S. Krishnakumari, antidiabetic effect of t. arjuna  bark extract in alloxan induced diabetic rats, Indian Journal of Clinical Biochemistry, 2006 / 21 (2) 123-128 .
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18)    Shah, C.S., Bhavsar, G.C., 1956. Pharmacognosy of the bark of Terminalia  tomentosaW&Aand comparison with Terminalia arjunaW&Abark. IndianJournal of Pharmacology 18, 81–84.
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