A review on pharmacological activity of Terminalia chebula

Description of the plant

The tree is between 50 and 80 feet tall. Its top is rounded, and its limbs are widely spaced. The bark has a few longitudinal fissures and is a dark brown colour. The ovate, elliptical leaves have two large glands close to the summit. The terminal spikes or short panicles of monoecious, dull white to yellow blooms are held in the centre and have an offensive, pungent odour. Flowers bloom in May through June, and fruit is visible from July through December. The fruit, sometimes known as a drupe, is one to two inches in size. There are five ribs or lines on the skin's surface. Green fruit is unripe, while yellowish-gray fruit is ripe. Fruit formation started in November, and fruits were gathered between January and April (The Ayurvedic pharmacopoeia of India, 2001).5

Special identity

Taxonomy of Terminalia chebula Retz

Names given to T. chebula Retz by local:. English: "Chebulic myrobalan"; Assamese: "shilikha"; Bengali: "haritaki"; Gujrati: "hardi, harde"; Hindi: "hara"; Kannada: "alale"; Konkani: "ordo, hardi"; Malayalam: "katukka"; Manipuri: "Manali"; Marathi: "hirda"; Oriya: "karadha Kata-K-Kay in Tamil; Haejarad in Urdu. The Sub-Himalayan pathways leading from the east to West Bengal and Assam contain T. chebula, which grows as high as 1,500 m in the Himalayas. This tree can be found in abundance in Madras, Mysore, and the southernmost region of the Bombay presidency. It also grows wild in Bengal, the central provinces of India, and the northern woods of India (Gupta et al.,2003).6

Classification based on T. chebula fruit size: Survariharade, a 2 inch long, big, dense, and heavy yellowish brown object; Rangariharade: These measure about an inch in length, are less furrowed and wrinkled than Survariharade, and have a yellow epidermis. Balaharade is smaller than the previous two types and has an epidermis that is dark or brown and extremely wrinkled. The smallest of all the characters is called Java harade; the other characters are comparable to Balaharade.

Classification of fruit growth When the size is similar to a cumin seed, it is called zira; Javi: When it is the same size as a grain of barley; Zangi: When it is of a raisin's size; Chini: Fruit that is somewhat firm with a greenish-yellow colour. Asfer - just before full development; Kabul –when it is fully developed (Sukhdev et al.,1999).7

Varieties

Bhavamisra describe seven different varieties of Terminalia chebula (Sastry et al.,2005).8

Antidiabetic activity   

Strong intestinal maltase inhibitory activity of Terminalia chebula fruit extract in rats did not affect intestinal sucrase or isomaltase activity, but its inhibitory effect on -glucosidase indicates that it may be effective for treating type 2 diabetes (Sabu et al.,2002).10

In both short- and long-term experiments, T. chebula fruit and seeds reduced blood glucose levels in streptozotocin-induced diabetic rats in a dose-dependent manner. They also displayed reno protective behaviour (kumar et al., 2009 and Kannan et al.,2012).11, 12

Anticarcinogenic activity

When the phenolics of Terminalia chebula fruit were studied, chebulinic acid, tannic acid, and ellagic acid were shown to have the highest growth-inhibitory effects on cancer cell proliferation (Saleem et al.,2002).13 Chebulinic acid, tannic acid, and ellagic acid were discovered to be the greatest cancer cell growth-inhibitory phenolics in T. chebula, according to a team of researchers that examined the fruit's phenolics' effects on the growth of the disease-causing cells (Saleem et al., 2002).13 The T. chebula fruit's ethanol extract was found to have effects on human (MCF-7) and mouse (S115) breast cancer cell lines, human osteosarcoma cell line (HOS-1), human prostate cancer cell (PC-3) and a non-tumorigenic immortalised human prostate cell (Reddy et al., 2009).14

Antiviral activity

Additionally, it has been noted that T.chebula shows modest effectiveness against HSV-1, HIV-1, and CMV (Yukawa et al.,1996). 15

The T. chebula extract displayed strong anti-HSV-1 efficacy when coupled with acyclovir. It raised the mean survival times of infected mice and decreased the occurrence of skin lesions at doses suitable for human use when compared to acyclovir and mice treated only with the herbal extract (p0.01 and p0.05) (Kurokawa et al.,1995). 16

Fruits from Terminalia chebula contained gallic acid, three galloyglucoses, and four HIV-1 integration inhibitors. Significantly inhibiting the compounds' 3'-processing of HIV-1 integrase is their galloylmoiety. (Ahn et al., 2002).17

The fruits of T. chebula provided three galloyl glucoses and GA (I), four HIV-1 integrase inhibitors (II-IV). Their galloyl moiety significantly contributes to the compounds' suppression of HIV-1 integrase's 3'-processing (Jeong et al.,2002).18 The retroviral reverse transcriptase inhibitory activity of T. chebula is also present (Lee et al., 2011).19

Haritaki (T. chebula) in vitro study against SARS-CoV2 may require screening (Dâmaris et al., 2020).20 Biomolecules from some Terminalia chebula plant species have already been shown to have antiviral properties.

Chebulagic and chebulinic acids exhibit superior direct antiviral action against HSV-2 compared to acyclovir and are more successful at preventing virus attachment and penetration to the host cells. In order to prevent sexually transmitted HSV-2 infection, it may therefore be a good candidate for alternative therapy (Kesharwani et al., 2017).21

IAV (the influenza A virus) replication can be efficiently stopped by chelating acids chebulinic and chebulagic. These substances exhibit antiviral effectiveness against both oseltamivir-resistant and wild-type IAV strains by acting as neuraminidase inhibitors (Li et al., 2020).22 In vitro influenza is inhibited by chebulagic acid and/or its hydrolysis products as a novel drug that recovers M2(S31N)-expressing yeast development. Without reference to the M2 (Duncan et al., 2020).23

Cardiotonic & cardioprotective activity

Several extracts made from the Terminalia chebula fruit rind have demonstrated cardiotonic action when tested on healthy and hypodynamic isolated frog hearts. Without altering heart rate, the extracts increased cardiac output and force of contraction. (Reddy et al.,1990).24 Pretreatment with T. chebula extract was observed to reduce the impact of the medication on the production of lipid peroxide and maintain the activity of the diagnostic marker enzymes in rats with isoproterenol-induced heart injury (Suchalatha et al., 2004).25 In an isolated frog heart model, its pericap has also been shown to have cardioprotective effects (Reddy, 1990).24

Anti-bacterial activity

A variety of bacterial species were resistant to Terminalia chebula antimicrobial properties (Ahmad et al.,1998).26 One team of researchers discovered that it is efficient in preventing Helicobactorpyroli (H. pyroli), a common bacteria linked to the emergence of gastritis, ulcers, and stomach malignancies, from producing urease (Malckzadehet al.,2001).27 Its antimicrobial properties include those against bacteria, fungi, protozoa, anthelmintics, and salmonella (Denis et al.,2021).28 Sharma et al., 201229 evaluated the antimicrobial efficacy of acetone, ethanol, methanol, hot aqueous and cold aqueous extracts of fruits of T.chebula against ear pathogens i.e. S.aureus, Acinetobacter sp., P.aeruginosa, P.mirabilis, E.coli and C.albicansand found that all extracts were effective against pathogens causing ear infections.

In another study by Singh et al.(2012) 30, the therapeutic effect of ethyl acetate, acetone, methanol and water extracts of fruits of T.chebula against several human pathogens (S.auerus, S.mutans, S.pyrogens, S.pneumoniaand S.aeruginosa) have been known. The aqueous extract of T.chebula Retz. Fruit also showed inhibitory effect against B.subtilis, S.aureus, S.epidermis, E.coli, P.aeruginosa and Staphylococcus flexineria (Kumar et al.,2009). 11 Agarwal et al. (2010), 31 studied the antibacterial activity of hydro-alcohalic fruit extract of T.chebula against microorganisms. B.subtilis, B.cereus, S.aureus, S.epidermis, E.coli, P.aeruginosa, S.flexineria and found that extract was effective against all test organisms. It is well known that tannins have antibacterial properties and can stop the growth of many bacterium, yeast, and fungal virus strains. The fruit of the Terminalia Chebula has shown antibacterial effectiveness against specific clinical strains of pathogens (Zhang et al.,2019).32 By combining methanolic, aqueous, and ethyl acetate extracts with a variety of standard antibiotics, the potential of T. chebula fruit extract was examined. The extracts demonstrated significant antibacterial action against the bacterial causes of all autoimmune inflammatory disorders (Mandeville et al.,2018).33

Antifungal activity

Aqueous Terminalia chebula extract shown antifungal efficacy against several yeasts and dermatophytes. The alcoholic ethyle acetate extract shows the activity against Aspergillus niger, aspergillus flavus, alternate. 70% of methanol ethylacetate, hexane, chloroform extract shows activity against Fusarium oxysporum, Phytopthoracapsici, Fusarium solanietc (Dutta et al., 1998 and Mehmood et al., 1999).34, 35

It is effective against the Dermatophytes, Epidermophyton floccosum, Microsporum gypseum, and Trichophyton rubrum as well as the pathogenic yeast Candida albicans (Barazani et al., 2003).36

Additionally, its inhibition of three yeasts (Candida spp.) and three dermatophytes (Trichophyton spp.) (Mehmood et al., 1999).35 Three yeasts (Candida spp.) and three dermatophytes (Trichophyton spp.) were inhibited by an aqueous preparation of T. chebula galls (Barazani et al., 2003).36 T. chebula methanol extract demonstrated in vitro anti-candidal action against Candida albicans that were resistant to clotrimazole (Bonjar, 2004).37 A seed extract was effective against the fungus Trichophyton glabrata. (Barazani et al., 2003).36

Antioxidant activity

Antioxidants are substances that stop oxidative chain reactions from spreading, hence preventing the oxidation of vital biomolecules (Kumar et al.,2020).38

Rats can benefit from the radioprotective and antioxidant characteristics of Terminalia chebula fruits. In cultured rat primary hepatocytes and rat liver, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage has also been shown.It has been demonstrated that a fruit extract from Terminalia chebula possesses preventive properties (Naik et al.2004).39 The fruit of the Terminalia chebula showed antioxidant activity in six extracts and four compounds, all to varying degrees (Cheng et al.,2003).40 Its fruit has anti-inflammatory and radioprotective effects on rats (Naik et al., 2004).39 Furthermore, the protective effects of the Terminalia chebula fruit extract against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury on cultured rat primary hepatocytes and rat liver have been linked (Lee et al.,2005 and Lee et al.,2007).41, 42

Cytoprotective activity

On the HEK-N/F cells, the fruit of Terminalia chebula ethanolic extract demonstrated a strong cytoprotective effect. Additionally, its extract demonstrated a sizable cytoprotective effect against oxidative damage brought on by UVB. Southern blot examinations of DNA extracted from sub-culture passages showed that Terminalia chebula had an inhibitory effect on the age-dependent shortening of the telomere length, which was attributed to these findings (M.Na et al.,2004).43

Gallic acid (GA) and caffeic acid (CA) were extracted as the active ingredients that prevented the cytotoxic Tlyphocyte-mediated cytotoxicity from the herbal remedy Kashi (myrobalan, the fruit of T. chebula). In addition, GA and CA blocked granule exocytosis in response to anti-CD3 stimulation when used in the same dosages. (Chang et al., 2010).44

Antimutagenic, radioprotective and chemopreventive activity

Aqueous extract and hydrolyzable tannins from T. chebula have been shown to have an antimutagenic action on Salmonella typhimurium (Grover et al.,1992).45 Gamma radiation was used to damage the DNA from the plasmid PBR322, however an aqueous extract of T. chebula prevented the strand breaks that ensued (Naik et al., 2004).39 Prior to receiving a whole-body radiation dose, mice that had received an aqueous extract of T. chebula displayed decreased radiation-induced DNA damage and lessened hepatic membrane lipid peroxidation. Furthermore, it protected human cells from gamma radiation harm when their DNA was exposed in vitro. (Gandhi et al.,2005). 46

Antiprotozoal activity

In experiments on amoebic liver in hamsters and caecalamoebiasis in rats, Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, and Zingiber officinale were combined with T. chebula to produce a maximum cure rate of 73% and 89%, respectively (Sohni et al.,1995; Dwivedi et al., 2008). 47, 48 T. chebula seeds' acetone extract displayed anti-plasmodial efficacy against Plasmodium falciparum (Bagavan et al.,2011). 49

Anti-inflammatory and anti-arthritic activity

T. chebula dried fruit extract demonstrated anti-inflammatory properties by preventing the production of inducible nitric oxide (Moeslinger et al.,2000).50 Animals with arthritis caused by collagen developed much more slowly after being given immature T. chebula seeds. (Nair et al.,2010).51 When included in a polyherbal formulation, T. chebula has demonstrated a dose-dependent anti-inflammatory effect to treat Freund's adjuvant-induced arthritis in rats (Aller-7) (Pratibha et al.,2004).52 Studies suggest that tissue protein denaturation, which generates autoantigens, may be associated with inflammatory and arthritic diseases (Liu et al., 2019).53

Adaptogenic and antianaphylactic activities

In an research administration of T. chebula extract after inducing anaphylactic shock decreased serum histamine levels, demonstrating the plant's potent anti-anaphylactic activity (Shin et al.,2001).54 Rats' peritoneal mast cells greatly enhanced their production of tumour necrosis factor-alpha when exposed to T. chebula water-soluble fraction, confirming the plant's potentially anaphylactic activity (Shin et al.,2001).54

Hypolipidemic and hypocholesterolemic acivity

T. chebula extract has been shown to have established hypolipidemic efficacy against experimentally generated athersclerosis (Maruthappan et al.,2010).55 Additionally, it had hypocholesterelomic action against rabbit atherosclerosis and hypercholesterolemia brought on by cholesterol (Israni et al.,2010).56

Gastro-intestinal motility improving and antiulcerogenic activity

Although T. chebula fruit has a long history of usage as a laxative, studies have shown that it can speed up stomach emptying (Tamhane et al., 1997).57 As Brunner's gland's secretory state improved, it emerged that this action was counterbalanced by a protective impact on the gastrointestinal mucosa, which plays a role in the prevention of duodenal ulcers (Sharma et al., 2011). 58

Anti-spasmodic activity

One of the numerous studies on T. Chebula, abnormal blood pressure, and intestinal spasms all decreased, indicating the herb's "anti-vata" or "anti-spasmodic" properties. This proves its continuous effectiveness for digestive issues including spastic colon and others (Seyyed et al., 2011).59