INTRODUCTION:

According to World Health Organization, about 80% of world population relies chiefly on plant based traditional medicine for their primary healthcare need. The medicinal plant Terminalia chebula Retz. and Willd. commonly known as Yellow myrobalan or Chebulic myrobalan or Haritaki is native to South Asia from India and Nepal east to southwest China (Yunnan) and south to Sri Lanka, Malaysia, and Vietnam. More than 100 species belong to the genus Terminalia which are big trees and they are found in different tropical regions of the world. The trees that belong to this genus “Terminalia” are known as a good secondary source of metabolites like cyclic triterpenes and derivatives, flavonoids, tannins and other aromatic metabolites. The genus of this plant comes from the latin word “terminus”, as the leaves of the tree are located at the terminal part of the branches. It is extensively used in Ayurveda, Unani, Amchi and Homeopathic medicine. Terminalia chebula is a popular traditional medicine not only used in India but also in other countries of Asia and Africa. This is used in traditional medicine due to the wide spectrum of pharmacological activities associated with the biologically active chemicals present in this plant. The observed health benefits may be credited to the presence of the various phytochemicals like polyphenols, anthocyanins, terpenes, flavonoids, alkaloids and glycosides. The purpose of this review is to gather the available traditional knowledge in the texts as well as published information on pharmacological and phytochemical analysis of the extracts and some of the isolated compounds of this plant as well as their toxic effects for highlighting the importance of this important medicine for use in human medical problems and maintenance of health.

Botanical group:

Kingdom: Plantae, Division: Magnoliophyta, Class: Magnoliopsida, Order: Myrtales, Family: Combretaceae, Genus: Terminalia (the leaves of the tree are located at the terminal part of the branches), Species: chebula (distorted from of the word Kabul) Retz.

Vernacular names:

Arabian: Haleelaz, Assamese: Xilikha, Hilikha, Bengali: Horitoky, Chinese: He Zi, English: Chebulic Myrobalan, Yellow/Black myrobalan, Ink tree, Farsi: Haleel, Gujarati: Harade, Himmej, Hindi: Harad or Harade, Kannada: Alale, Analekai, Malayalam: Kadukai, Marathi: Hirada, Odia: Harida, Sanskrit: Haritaki, Tamil: Kadukkai, Telugu: Karakkaya, Kaduka, Tibetan: A-ru-ra.

Synonyms in Ayurveda:

Various names are given to Terminalia chebula Retz. and Willd in Ayurveda due to its multiple characteristics like Haritaki, Abhaya, Amruta, Haimavati, Shiva, Pathya, Pachani, Rohini, Kayastha, Shreyasi, Vijaya, etc. based on its different pharmacological actions and qualities.

Morphology of the plant:

Terminalia chebula Retz. and Willd. is a medium to large deciduous tree, younger stems glabrescent, woody growing upto 30 m (98 ft) tall, with a trunk up to 1 m (3 ft 3 inch) in diameter. Leaves: Alternate to sub-opposite in arrangement, simple; exstipulate; petiolate; oval, laminae broadly elliptic to elliptic–oblong, rarely ovate, 7 to 8 cm (2.8 to 3.1 inch) long and 4.5 to 10 cm (1.8 to 3.9 inch) broad with a 1 to 3 cm (0.39 to 1.18 inch) petiole, the bases obtuse/cordate, the margins entire, the tips acute, glabrescent/glabrous above with a yellowish pubescence below. The fruit is drupe-like, 2 to 4.5 cm (0.79 to 1.77 in) long and 1.2 to 2.5 cm (0.47 to 0.98 in) broad, blackish, with five longitudinal ridges. Inflorescence: Its paniculate spikes, terminal and axillary; peduncles tomentose; bracts subulate, small, caducous. Flowers: These are 2 mm long, 3-4 mm in diameter; bracts nearly glabrous, 1.5-2.0 mm long; calyx outside glabrous, inside densely villous, calyx-segments triangular; stamens 3-4 mm long; ovary glabrous, ovoid, 1 mm long; style glabrous, 2.5-3.0 mm long. The dull white to yellow flowers are monoecious, and have a strong, unpleasant odour. They are borne in terminal spikes or short panicles.Fruit: It is a drupe, glabrous, sub globose to ellipsoid/ovoid, 2.5–5.0 cm by 1.5-2.5 cm, usually smooth or frequently 5-angulate, ridged, wrinkled, yellow to orange-brown in colour turning blackish when dry. Fruits contain astringent substances-tannic acid, Chebulinic acid, gallic acid etc. Resin and a purgative principle of the nature of anthraquinone and sennoside are also present. Seed: one, rough, ellipsoid, 1.0-2.0 cm by 0.2-0.7 cm and without ridges.

Geographical Distribution and habitat:

Terminalia chebula is found throughout South East Asia like India, Sri Lanka, Bhutan, Nepal, Bangladesh, and Pakistan, Myanmar, Cambodia, Laos, Vietnam, Indonesia, Malaysia, Egypt, Philippines, Turkey and Thailand. In China, native in W Yunnan; cultivated in Fujian, Guangdong, Guangxi (Nanning), and Taiwan (Nantou). In India, it is found in the Sub Himalayan tracks from Ravi eastwards to West Bengal and Assam, ascending up to the altitude of 1500 meter in the Himalayas. This tree is wild in forests of Northern India, central provinces and Bengal, common in Madras, Mysore and in the southern part of the Bombay presidency¹. Flowers appear from April to August and fruits ripen from October to January.

Propagation, planting and harvesting:

Trees are generally grown from seeds. The fallen fruits are collected and dried thoroughly first. Later the hardened flesh is removed. Fermentation of the stones gives the best germinative results, but clipping the broad end of the stone without damaging the embryo, followed by soaking in cold water for 36 hours gives good results too. In India, seeds are usually sown in boxes or nursery beds in spring or before the rainy season, covered with soil, and watered regularly. Clay and sandy soils are ideal for growing them. They require full sunlight and ample amount of water for growing properly. A mere 20% success is reported. Transplanting from the nursery into the field can be done in the first or second rainy season. Shading is desirable in early stages in the nursery and after transplanting. Propagation by cuttings is possible, but less successful than transplanting nursery-raised seedlings. These trees cannot tolerate cold temperatures below 16^oC. In the forest, regeneration is facilitated by creating small gaps in the canopy, and this may be supplemented by sowing seeds in the clearings.These deciduous trees remain leafless from February to early April. The flowers bloom between April and August. The trees bear fruits between November and February. The fruits are harvested while they are ripended. Harvesting is done by handpicking the fruits.

Varieties as per shape of fruit as mentioned in Ayurveda (7 types):

Vijaya variet is of alabu shape and used in all diseases which are available in Vindhya mountains. This is considered as best among 7 varieties. Rohini variety is circular in shape, useful in wound healing, available in Pratishtanaka, Jhansi and other parts of Madhya Pradesh. Putana variety is having small fruits with big seeds, used for external application and are available in Sindha area. Amruta variety is having thick fruit pulp, useful for panchakarma (detoxification) and is available in Champa, Bhagalpur area. Abhaya variety is having five creases in fruit skin, useful in eye disorders and is available in Champa, Bhagalpur area. Jivanti variety is having yellow coloured fruit, useful in all diseases and available in Saurastra region of Gujarat. Chetaki variety is having the creases in fruit skin which is useful for purgation and is available in Himachal Pradesh².

In fact only two types of Haritaki are available. The big variety, available everywhere and used in the preparation of Ayurvedic proprietary medicine, is the Vijaya variety, useful for both rejuvenation and purificatory purposes. The small variety (trade name-Jangi haritaki) is the Chetaki variety mentioned in the classics. These are immature, unripe, small, stoneless fruits used for purgative purpose³.

Uses in Ayurveda as per various dosage form:

Chewing the Haritaki fruit causes increase in digestion power whereas if it is made into a paste and eaten, it clears and cleanses bowel. If it is steamed or boiled, it becomes absorbent, useful in malabsoption symdrome.

If it is fried and used, it is useful in Tridosha imbalance conditions. Haritaki if eaten after food, it heals to eliminate all toxic effects due to food poisoning. If it is taken along with salt, it balances kaphs, whereas if taken with sugar, it balances pitta and if taken with ghee, it balances vata disorders².

Chemical composition:

A number of glycosides have been isolated from Terminalia chebula, including the triterpenes arjunglucoside I, arjungenin, and the chebulosides I and II. Other constituents include a coumarin conjugated with gallic acids called chebulin, as well as other phenolic compounds including ellagic acid, 2,4-chebulyl-β-D-glucopyranose, chebulinic acid, gallic acid, ethyl gallate, punicalagin, terflavin A, terchebin, luteolin, and tannic acid^4,5. Chebulic acid is a phenolic acid compound isolated from the ripe fruits^6,7. Luteic acid can be isolated from the bark⁸. T. chebula also contains terflavin B, a type of tannin, while chebulinic acid is found in the fruits⁹.

Other constituents:

The major bio-active constituents of the fruit are tannins, anthraquinones, chebulinic acid, chebulagic acid, chebulic acid, ellagic acid and gallic acid. The other minor compounds include corilegin, β-D-glucogallin, glucose and sorbitol. Polyphenolic compounds, triterpene glycosides, terchebulin, punicalagin, terflavin A, flavonoids, reducing sugars and starch are other constituents of the fruit. Terpenene glycosides, arjungenin and arjunglucoside-I. 18 amino acids and a small quantity of phosphoric, succinic, syringic and quinic acids.

Medicinal qualities and Systemic use as in Ayurvedic classics:

Rasa-Five types of tests except lavana (salt) i.e. seed kernel is Madhura (sweet), pulp of fruit is Amla (sour), skin is Katu (punjent), fruit rind is Tikta (bitter) and Seed is Kasaya (astringent) but there is dominancy of Kashaya rasa. Guna or quality is laghu (light) and ruksha (dry), Virya or potency is ushna (hot), Vipaka is sweet (Madhura), Doshakarma: Alleviates vitiation of all 3 doshas i.e.Tridosha hara due to sweet, bitter and astringent tastes, it balances pitta, due to its pungent, bitter and astringent tastes, it balances kapha and due to its sweet and sour taste, it balances vata dosha.

External uses: Local application of Haritaki is Anti-inflammatory. In conjunctivitis it can be used for application on eyelids. A decoction of Haritaki is used for wound and also used for gargaling in the diseases of mouth and throat.

Digestive System: Due to Anulomana karma it helps in normalizing bowel movements. (Haritaki 1 to 3 grams is administered with a cup of hot water to relieve ama (undigested food constituents) in case of Irritable Bowel Disease associated with low digestive power).Further, useful in loss of appetite, vomiting, pain in abdomen, early stage of ascites, Hemorrhoids, Hepatomegaly, Splenomegaly and parasitical infestation. If the bark of Haritaki if eaten properly with chewing in mouth, it improves digestion. Powdered Haritaki reduces constipation in a dose of 3-6 gm. A fine powder of Haritaki is used as a tooth powder which strengthens the gums. Purgation induced by Haritaki is relived by its own. Bala Haritaki (small variety) is useful in hemorrhoids. Useful in piles/hemorrhoids by reducing the size of pile mass and bleeding. (Sitz bath with 2 table spoon of haritaki powder in 10 liters water for 10 minutes, before bath, is useful in reducing the swelling and healing). 10 g of Haritaki powder with grapes may be taken to get relief in hyperacidity ¹⁰. 10-15 g of dry Haritaki or Triphala i,e. Powder of Hairtaki (Terminalia chebula), Vibhitaki (Terminalia bellerica) and Amalaki (Phyllanthes emblica) in equal quantities with warm water may be consumed after dinner to relieve constipation ². Useful in spleenomegaly (3 to 5 gram once or twice a day is administered with 2 to 3 grams of jiggery)¹¹.

Circulatory System: As Haritaki is raktagami (exhibiting much action on Rakta Dhatu), it is used in weakness of Heart, Vatarakta (gout) and other disorders of the blood. Cures anemia (5 gram of Haritaki powder to be taken and mix well with equal quantity of jaggery powder to form a bolus. 2 bolus twice daily after meals for 60 days is to be consumed)¹², Haritaki is useful to reduce anemia ¹³, useful in jaundice and oedma.

Respiratory System: Rhinitis, Cough, Hoarseness of voice, Hiccups and Dyspnoea, COPD, wheezing, breathing difficulty are releaved by Haritaki as it reduces congestion.

Reproductive System: Useful in Shukrameha, Leucorrhoea and acts as a uterine tonic.

Urinary System: Useful in Dysurea, retention of urine, Calculus (Haritakyadi sidha Dugdha) and urinary tract disorders, useful in diabetes (every morning and evening, 1 tea spoon of Haritaki powder with a little honey may be consumed. Constant intake of Haritaki helps to control diabetes)¹⁴.

Nervous System: Useful in headache, weakness of the nerves and the brain, as well as in Vata disorders and diminished vision and improves intelligence (Medha).

Skin: Useful in Erysipelas and other skin disorders, Haritaki prevents accumulation of pus in skin diseases and acts as a Rasayana. Haritaki with oil is extremely helpful in healing of wounds especially in burns. It helps to improve skin complexion.

Rasayana: Antiageing, rejuvenative, nourishing (after removing seeds of 2 to 4 dry Haritaki fruits, it may be cut in to 2 to 3 pieces followed by cooking in 4 parts of milk till it becomes soft. After cooling, little ghee and honey will be added. This recipe may be prepared daily and consume to attain good immune power)¹⁵, improves body weight (Bruhmani), improves life expentency/span by maintaining healthyness (Ayushya). Haritaki acts as a rejuvenator (by clearing the mala present in the body). For the purpose of rasayana karma (rejuvenation, anti ageing purpose), Haritaki is taken along with different ingredients in different seasons (ritu) which is popular as Ritu Haritaki. In rainy season (varsa ritu), Haritaki is given along with saindhava (rock salt), in autumn season (sarat ritu), haritaki is given along with sarkara (sugar), in early winter (hemanta ritu), haritaki is given along with sunthi (ginger), in winter (sisira ritu), haritaki is given along with pippali (long pepper), in spring season (vasanta ritu), haritaki is given along with madhu (honey) and in summer (greshma ritu), haritaki is given along with guda (jaggery). Dose: 2-4 gm for Rasayana action. It causes natural detoxification of bodily toxic materials.

Medicines in market:

Abhayarishta, Triphala Churna, Agastya rasayana, Brahma rasayana, Dashamoola Haritaki etc.

Side effects and contraindications:

Though Haritaki has immense health benefits, due to its astringent and hot nature, it is contraindicated in few cases. Haritaki is best avoided in Adhva and Ati Khinna (people who have walked for very long and who are tired). Balavarjita (who have depleted immunity and strength), Rooksha (who are feeling dry and are emaciated), Krusha (having lean body), Langhanakarshita (who have fasted for long), Pittadhika (in people with increased Pitta/burning sensation), Garbhavati (in pregnant woman), Vimuktarakta (after blood letting treatment), during and soon after menstruation, Kshut (hungry), Trishna (thirsty), Ushnarta (who are having severe thirst, hunger and have got exposed to Sun for long), Ajeerna (in patients suffering from indigestion), Strimadya karshita (those who are emaciated due to increased sexual activity and alcohol), Mukshashosha (in people having dry mouth), Hanusthambha (in people with neck stiffness), Galagraha (in people with dry throat), Navajvara (in early stages of fever) etc. Though there are a few nutritive health benefits, Haritaki is more of cleansing, moisture absorbing, weight reducing in nature. Hence it is advised to avoid during pregnancy. In most of the contraindications explained above, all have dryness, lack of water supply kind of symptoms. Haritaki, already being astringent, is not advisable because it may further contribute to dryness. Haritaki is best avoided in infants, upto 5 years of age. It should be given under medical supervision in children. Single herb usage of Haritaki is contra indicated in lactating mother. It may decrease breast milk production.

Haritaki in Tibetan medicine:

Haritaki is named as a-ru-ra, ‘a’ means best of medicines and cures all diseaess caused by tridosha (vata, pitta and kapha, 3 physiological body elements), ‘ru’ means the fruit has flesh, bone and skin which clears diseases due to imbalance of tridosha and ‘ra’ means it’s body is like that of rhinocerous and clears the diseases from all dhatus (7 anatomical body constituents). Hariraki is called as ‘man-mchog-rgyal-lo’ means king of the best of medicines^{16, 17}.

Pharmacological activity:

1. Antioxidant and free radical scavenging activity:

i) The leaves, bark and fruit of Terminalia chebula possessed high antioxidant activity and phenolics were found to be responsible for this activity¹⁸

ii) Aqueous extract of Terminalia chebula inhibited xanthine/xanthine oxidase activity and was also an excellent scavenger of DPPH radicals¹⁹

iii) Terminalia chebula in a polyherbal formulation (Aller-7/NR-A2) inhibited free radical induced hemolysis and also significantly inhibited nitric oxide release from lipopolysaccharide stimulated murine macrophages²⁰.

iv) Six extracts and four compounds of Terminalia chebula fruit exhibited antioxidant activity at different magnitudes of potency²¹.

v) Strong antioxidant activity of aqueous extract of Terminalia chebula was observed by studying the inhibition of radiation induced lipid peroxidation in rat liver microsomes at different doses²², Methanolic extract was also found to inhibit lipid peroxide formation and to scavenge hydroxyl and superoxide radicals in vitro²³. Acetone extract has stronger antioxidant activity than alpha-tocopherol and HPLC analysis with diode array detection indicated the presence of hydroxybenzoic acid derivatives, hydroxycinnamic acid derivatives, flavonol aglycones and their glycosides, as main phenolic compounds²⁴.

vi) An evaluation of extracts of five traditional medicinal plants viz, Quercus infectoria Olive., Terminalia chebula Retz., Lavendula stoechas L., Mentha longifolia L., Rheum palmatum L from Iran on the inhibition of mushroom tyrosinase activity and scavenging of free radicals. In general Q. infectoria and T. chebula significantly inhibited tyrosinase activity and DPPH radical. Both activities were concentration-dependant but not in linear manner. It is needed to study the cytotoxicity of these plant extracts in pigment cell culture before further evaluation and moving to in vivo conditions²⁵

2. Anticarcinogenic activity:

i) A group of researchers have reported the inhibitory action on cancer cell growth by the phenolics of Terminalia chebula Retz fruit and found that chebulinic acid, tannic acid and ellagic acid were the most growth inhibitory phenolics of T. chebula²⁶.

ii) Ethanol extract of Terminalia chebula fruit inhibited cell proliferation and induced cell death in a dose dependent manner in several malignant cell lines including human (MCF-7) and mouse (S115) breast cancer cell line, human osteosarcoma cell line (HOS-1), human prostate cancer cell (PC-3) and a non-tumorigenic immortalized human prostate cell line (PNT1A). Besides, acetone extract of bark and fruit powder of Terminalia chebula harbors constituents with promising anticarcinogenic activity Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line²⁷

3. Antimutagenic, radioprotective and Chemopreventive activity:

i) Antimutagenic activity of aqueous extract and hydrolyzable tannins from Terminalia chebula in Salmonella typhimurium has been documented²⁸

ii) Gamma radiation induced strand breaks formation in plasmid PBR322 DNA was inhibited by aquesous extract of Terminalia chebula¹⁹.

iii) The administration of aqueous extract of Terminalia chebula prior to whole body irradiation of mice resulted in a reduction of peroxidation of membrane lipids in the mice liver as well as a decrease in radiation induced damage to DNA. It also protected the human lymphocytes from undergoing the gamma radiation-induced damage to DNA exposed in vitro²⁹.

iv) Terminalia chebula showed chemopreventive effect on nickel chloride -induced renal oxidative stress, toxicity and cell proliferation response in male Wistar rats³⁰.

4. Hepatoprotective activity:

i) A mixture of chebulic acid (CA) and its minor isomer, neochebulic acid with a ratio of 2:1 isolated from ethanolic extract of Terminalia chebula fruits showed strong hepatoprotective activity³¹.

ii) Ethanol extract of Terminalia chebula was found to prevent the hepatotoxiocity caused by the adminstration of rifampicin, isoniazid and pyrazinamide (combination) in sub-chronic model (12 weeks)³².

iii) Protective effects of an aqueous extract of Terminalia chebula fruit on the tert-butyl hydroperoxide-induced oxidative injury was observed in cultured rat primary hepatocytes and rat liver have also been documented ^{22, 23}done

iv) Terminalia chebula in an herbal formulation (HP-1) showed hepatoprotective activity against carbon tetrachloride induced toxicity in rat hepatocytes³³.

5. Cardioprotective activity:

Terminalia chebula extract pretreatment was found to ameliorate the effect of isoproterenol on lipid peroxide formation and retained the activities of the diagnostic marker enzymes in isoproterenol induced myocardial damage in rats.³⁴ Its pericap has also been reported to have cardioprotective activity in isolated frog heart model³⁵.

6. Cytoprotective activity:

i) Gallic acid (GA) and CA were isolated from the extract of the herbal medicine Kashi (myrobalan, the fruit of Terminalia chebula) as active principal that blocked the cytotoxic T-lyphocyte-mediated cytotoxicity. Granule exocytosis in response to anti-CD3 stimulation was also blocked by GA and CA at the equivalent concentrations³⁶.

ii) The ethanolic extract of Terminalia chebula fruit exhibited a notable cytoprotective effect on the HEK-N/F cells. In addition its extract exhibited significant cytoprotective effect against UV-induced oxidative damage. These observations were attributed to the inhibitory effect of the Terminalia chebula extract on the age dependent shortening of the telomere length as shown by the Southern Blots of the terminal restriction fragments of DNA extracted from sub-culture passages³⁷. It exhibited the development of duodenal ulcers and appeared to exert a cytoprotective effect on the gastric mucosa in vitvo³⁸.

iii) Cytoprotective effect on oxidative stress and inhibitory effect on cellular aging of its fruits have also been documented³⁹.

7. Antidiabetic and renoprotective activity:

i) Terminalia chebula fruit and seeds exhibited dose dependent reduction in blood glucose of streptozotocin induced diabetic rats both in short term and long term study and also had renoprotective activity^40,41.

ii) Water extract of dry fruits of Terminalia chebula at a dose of 200 mg/kg body weight improved the glucose tolerance as indicated by 44% of reduction in the peak blood glucose at 2nd hour in glucose tolerance test in diabetic (streptozotocin induced) rats.⁴² The fruit extract of Terminalia chebula exerts a significant and dose-dependent glucose lowering effect in the rat model of metabolic syndrome.⁴³

iii) Chebulagic acid, isolated form Terminalia chebula Retz, proved to be a reversible and non-competitive potent alpha-glucosidase inhibitor of maltase with a K (i) value of 6.6 muM. The inhibitory influence of chebulagic acid on the maltase-glucoamylase complex was more potent than on the sucrase-isomaltase complex. The magnitude of alpha-glucosidase inhibition by chebulagic acid was greatly affected by its origin. These results show a use for chebulagic acid in managing type-2 diabetes⁴⁴.

8. Antibacterial activity:

i) Terminalia chebula exhibited antibacterial activity against a number of both Gram-positive and Gram-negative human pathogenic bacteria⁴⁵.

ii) It is effective in inhibiting the urease activity of Helicobactor pyroli, an ubiquitous bacterium implicated in the development of gastritis, ulcers and stomach cancers⁴⁶. Ethanedioic acid and ellagic acid isolated from butanol fraction of Terminalia chebula fruit extract had strong antibacterial activity against intestinal bacteria, Clostridium perfingens and Escherichia coli⁴⁷.

iii) GA and its ethyl ester isolated from ethanolic extract of Terminalia chebula showed antimicrobial activity against methicillin-resistant Staphylococcus aureus (S. aureus)⁴⁸.

iv) Ripe seeds of Terminalia chebula also exhibited strong antibacterial activity against S. aureus⁴⁹.

v) The aqueous extract of Terminalia chebula strongly inhibited the growth of Streptococcus mutans, salivary bacteria⁵⁰.

vi) Diffusate of Terminalia chebula showed an inhibitory effect against strain X-100 of the bacterium Xanthomonas campestris pv.citri indicating its usefulness for the management of citrus canker disease which is a disease affecting citrus species of plants⁵¹.

vii) It has also growth inhibitory action against Salmonella typhi, ⁵² Klebsiella⁵³, Shigella⁴⁷ and intestinal bacteria^50.

viii) Growth inhibitory activity of active component from Terminalia chebula fruits against intestinal bacteria.⁵⁴

ix) Ethanol extract of Terminalia chebula fruit showed strong antibacterial activity against multidrug-resistant uropathogenic Escherichia coli and phenolics were found to be responsible for this antibacterial activity^55,56

x) A study on Terminalia chebula fruit extract treated cotton fabric for health care application showed anti microbial activity⁵⁷

9. Antifungal activity:

i) An aqueous extract of Terminalia chebula exhibited antifungal activity against a number of dermatophytes and yeasts^{58, 59}.

ii) It is effective against the pathogenic yeast Candida albicans and dermatophytes Epidermophyton, Floccosum, Microsporum gypseum and Trichophyton rubrum⁵⁸.

iii) Its inhibitory effect on three dermatophytes (Trichophyton spp.) and three yeasts (Candida spp.) has also been documented⁶⁰.

iv) An aqueous extract of galls of Terminalia chebula showed inhibitory effects on three dermatophytes (Trichophyton spp.) and three yeasts (Candida spp)

v) In vitro anticandidal activity of methanol extract of Terminalia chebula was observed against clotrimazole resistant Candida albicans⁶¹.

vi) Seed extract exhibited antifungal activity against Trichophyton glabrata⁵⁸

10. Antiviral activity:

i) Terminalia chebula fruits afforded four immunodeficiency virus type 1 (HIV-1) integrase inhibitors, GA (I) and three galloyl glucoses (II-IV). Their galloyl moiety plays a major role for inhibition against the 3′-processing of HIV-1 integrase of the compounds⁶².

ii) Terminalia chebula has also retroviral reverse transcriptase inhibitory activity.⁶³

iii) It protects epithelial cells against influenza A virus, supporting its traditional use for aiding in recovery from acute respiratory infections⁶⁴.

iv) The methanol and aqueous extracts of T. chebula showed a significant inhibitory activity with IC50≤5 µg/mL on human immunodeficiency virus-1 reverse transcriptase⁶⁵.

v) It also demonstrated the therapeutic activity against herpes simplex virus both in vitro and in vitvo tests⁶⁶.

vi) These finding prompted a team of Japanese researchers to investigate T. chebulas's effect on human cytomagalovirus (CMV). They found that T. chebula was effective in inhibiting the replication of human cytomagalovirus in vitro and in an AIDS model with immunosuppressed mice and concluded that it may be beneficial for the prevention of CMV diseases and immonocompronised patients⁶⁷.

vii) It is also helpful in sexually transmitted diseases and AIDS⁶⁸.

viii) Tannins from T. chebula are effective against potato virus x⁶⁹.

11. Antiprotozoal activity:

i) A combination of T. chebula and four other botanicals (Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, and Zingiber officinale) had a maximum cure rate of 73% in experimental amoebic liver abscess in hamsters⁷⁰ and 89% in experimental caecal amoebiasis in rats showing its antiamoebic activity against Entamoeba histolytica⁷¹

ii) The acetone extract of T. chebula seeds showed anti plasmodial activity against Plasmodium falciparum⁷².

12. Anti-inflammatory and anti-arthritic activity:

i) Aqueous extract of dried fruit of T. chebula showed anti-inflammatory by inhibiting inducible nitric oxide synthesis⁷³.

ii) Chebulagic acid from immature seeds of T. chebula significantly suppressed the onset and progression of collagen induced arthritis in mice⁷⁴.

iii) Terminalia chebula in a polyherbal formulation (Aller-7) exhibited a dose dependent anti-inflammatory effect against Freund's adjuvant induced arthritis in rats⁷⁵.

13. Anti-allergic activity:

i) Aller-7, a polyherbal formulation of seven medicinal plants including Terminalia chebula exhibited potent in vitro antiallergic activity in isolated guineapig ileum substrate⁷⁵.

14. Adaptogenic and antianaphylactic activities:

i) T. chebula fruit was one of the six Ayurvedic herbs administered to animals to test their adaptogenic potential. All six traditional rasayana plants were able to aid the animals against a variety of different stressors working in different ways⁷⁶.

ii) Besides, animal studies show that when extract of T. chebula was administered following induction of anaphylactic shock, the serum histamine levels were reduced, indicating its strong antianaphylactic action⁷⁷.

iii) Water soluble fraction of Terminalia chebula had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from rat peritoneal mast cells indicating its strong antianaphylactic action⁷⁷.

15. Hypolipidemic and hypocholesterolemic acivity:

i) Hypolipidemic activity of Terminalia chebula extract against experimentally induced athersclerosis have been documented⁷⁸.

ii) It also possessed hypocholesterelomic activity against cholesterol-induced hypercholesterolemia and atherosclerosis in rabbits⁷⁹.

16. Gastrointestinal motility improving and anti -ulcerogenic activity

i) Although its traditional use as laxative is well established, Terminalia chebula fruit has been shown to increase gastric emptying time⁸⁰.

ii) This action appeared to be balanced with a protective effect on the gastrointestinal mucosa, with the improvement in the secretory status of Brunner's gland involved in the protection against duodenal ulcer⁸¹.

iii) Comparison of enteroprotective efficacy of triphala formulations (Indian Herbal Drug) on methotrexate-induced small intestinal damage in rats and foundthat triphala unequal formulation provides significantly more protection against methotrexate-induced damage in rat intestine⁸².

17. Antispasmodic activity:

One of the numerous studies of Terminalia chebula demonstrated its ‘anti-vata’ or ‘anti-spasmodic’ properties by the reduction of abnormal blood pressure as well as intestinal spasms. This confirm its traditional usefulness for spastic colon and other intestinal disorders⁸³.

18. Anticaries activity:

The aqueous extract of Terminalia chebula strongly inhibited the growth, sucrose induced adherence and glucan induced aggregation of Streptococcus mutans. Mouth rinsing with a 10% solution of the extract inhibited the salivary bacterial count and glycolysis of salivary bacteria for upto 90 min post rinsing^{53, 84}.

19. Wound healing activity:

Topical administration of an alcoholic extract of Terminalia chebula leaves on the healing of rat dermal wounds showed that Terminalia chebula treated wounds healed faster as indicated by improved rates of contraction and decreased period of epithelialization⁸⁵

20. Purgative property:

Purgative action of an oil fraction from Terminalia chebula has been documented⁸⁶

21. Immunomodulatory activity:

Crude extract of Terminalia chebula stimulated cell-mediated immune response in experimental amoebic liver abscess in golden hamsters⁷⁰, aqueous extract of Terminalia chebula produced an increase in humoral antibody titer and delayed type hypersensitivity in mice⁸⁷

CONCLUSIONS AND RECOMMENDATIONS:

Terminali chebula is one of the most ingenious plants having a wide range of pharmacological and medicinal activities. This multifaceted medicinal plant is the distinctive source of various types of compounds having various chemical structures. Though it has a number of pharmacological activities due to the presence of various types of bioactive compounds, little work has been done on the probable medicinal applications of this plant against the diseases particularly on mutagenicity having radioprotective and Chemopreventive activity, immunomodulatory effect and role against multidrug resistant bacterial pathogens. Hence extensive investigation is needed to exploit its therapeutic ability to combat other various medical situations. Extensive study required for its bioactivity, mechanism of action, pharmacotherapeutics, toxicity, standardization, pre clinical trials and clinical trials for global safe use of this drug.

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Received on 25.06.2018 Modified on 12.07.2018

Res. J. Pharmacology and Pharmacodynamics.2018; 10(3):115-124.

DOI: 10.5958/2321-5836.2018.00023.X