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Positive effects on the liver

Terminalia Chebula: Liver

Scientific experiments and studies that underline the positive effects on the liver.

Haritaki extracts have been found to prevent hepatotoxicity in several studies. Hepatotoxicity is the property of chemical substances to be toxic to the functional cells of the liver (hepatocytes). These substances are called liver toxins or liver poisons. This effect has been attributed to the pronounced antioxidant and membrane stabilizing activities of Hairtaki.

Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway

Toxicol In Vitro. 2016 Aug;34:8-15. doi: 10.1016/j.tiv.2016.03.013. Epub 2016 Mar 25.

Advanced glycation end-products (AGEs) are formed during normal aging, and at an accelerated rate in metabolic syndrome patients. Nonalcoholic steatohepatitis (NASH) can be caused by the AGEs in plasma, while glyceraldehyde-derived AGEs (glycer-AGEs) are significantly higher in the serum of NASH patients. In this study, we investigated the molecular mechanisms of chebulic acid, isolated from Terminalia chebula Retz., in the inhibition of glycer-AGEs induced production of reactive oxygen species (ROS) and collagen accumulation using the LX-2 cell line. Chebulic acid significantly inhibited the induction of ROS and accumulation of collagen proteins by glycer-AGEs. ERK phosphorylation and total nuclear factor E2-related factor 2 (Nrf2) protein expression were induced by chebulic acid in a dose-dependent manner. Chebulic acid was also found to induce translocation of Nrf2 into the nucleus, which was attenuated by inhibition of ERK phosphorylation through treatment with PD98059. Following translocation of Nrf2, chebulic acid induced the protein expressions of catalytic subunit of ?-glutamylcysteine synthetase and glutathione synthesis. Collagen accumulation was also significantly reduced by chebulic acid treatment. The observed effects of chebulic acid were all inhibited by PD98059 treatment. Taken together, these results suggest that chebulic acid prevents the glycer-AGEs-induced ROS formation of LX-2 cells and collagen accumulation by ERK-phosphorylation-mediated Nrf2 nuclear translocation, which causes upregulation of antioxidant protein production.

Chebulic acid significantly inhibited the induction of ROS and accumulation of collagen proteins by glycer-AGEs. ERK phosphorylation and total nuclear factor E2-related factor 2 (Nrf2) protein expression were induced by chebulic acid in a dose-dependent manner.

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Hepatoprotective Effects of Different Extracts From Triphala Against CCl 4-Induced Acute Liver Injury in Mice

Front Pharmacol. 2021 Jul 5;12:664607. doi: 10.3389/fphar.2021.664607. eCollection 2021.

Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-a, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1. Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

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Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats

Veterinary Medicine and Science. 2021 Sep;7(5):1778-1785. doi: 10.1002/vms3.580. Epub 2021 Jul 20.)

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. Terminalia arjuna bark, an indigenous plant used in ayurvedic medicine in India, primarily as a cardiotonic is also used in treating diabetes, anemia, tumors and hypertension. The present study examined the effect of ethanolic extract (250 and 500 mg/kg body weight) of Terminalia arjuna stem bark in alloxan induced diabetic rats and its lipid peroxidation, enzymatic and nonenzymatic activity was investigated in the liver and kidney tissues. The extract produced significant (P<0.05) reduction in lipid peroxidation (LPO). The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. 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 (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.

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Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

BMC Complementary and Alternative Medicine 2006 Sep 30;6:33. doi: 10.1186/1472-6882-6-33.

Results showed that Carbon tetrachloride (CCI4) caused a marked rise in serum levels of GPT and ALP. TBARS level was also increased significantly whereas glutathione, superoxide dismutase, catalase and glutathione-S-transferase levels were decreased in the liver and kidney tissue homogenates of CCl4 treated mice. Aqueous extract of Termnalia arjuna successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. Conclusion: Our study demonstrated that the aqueous extract of the bark of Termnalia arjuna could protect the liver and kidney tissues against CCl4-induced oxidative stress probably by increasing antioxidative defense activities.

[Link to the scientific study]

Terminalia chebula (fruit) prevents liver toxicity caused by sub-chronic administration of rifampicin, isoniazid and pyrazinamide in combination

Human & Experimental Toxicology 2006 Mar;25(3):111-8. doi: 10.1191/0960327106ht601oa.

Terminalia chebula Gertn. (Combetraceae) is an important herbal drug in Ayurvedic pharmacopea. In the present study, a 95% ethanolic extract of T. chebula (fruit) (TC extract), which was chemically characterized on the basis of chebuloside II as a marker, was investigated for hepatoprotective activity against anti-tuberculosis (anti-TB) drug-induced toxicity. TC extract was found to prevent the hepatotoxicity caused by the administration of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) (in combination) in a sub-chronic mode (12 weeks). The hepatoprotective effect of TC extract could be attributed to its prominent anti-oxidative and membrane stabilizing activities. The changes in biochemical observations were supported by histological profile.

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Evaluation of the effects of the hydroalcoholic extract of Terminalia chebula fruits on diazinon-induced liver toxicity and oxidative stress in rats

Avicenna Journal of Phytomedicine Sep-Oct 2017;7(5):454-466.

Wistar rats were orally administered with 25 mg/kg body weight diazinon. Vehicle (distilled water) and silymarin (50 mg/kg body weight) were used as the negative and positive control groups, respectively. Diazinon-administered groups were treated with T.chebula (Terminalia chebula) fruit extract (200, 400, and 800 mg/kg). After 15 days of treatment, the blood specimens and liver samples were examined. Results: In diazinon-treated group, the levels of serum urea, high density lipoprotein (HDL), and liver superoxide dismutase (SOD), catalase (CAT), and vitamin C significantly decreased (p<0.05) compared to control. Also, in this group, serum triglyceride (TG), total cholesterol (TC), very low density lipoprotein cholesterol (VLDL), protein carbonyl (PC), malondialdehyde, tumor necrosis factor-a (TNF-a), and TNF-a gene expression significantly increased (p<0.05) as compared to the control (vehicle-treated rats). Treatment with T. chebula resulted in a significant increase (p<0.05) in CAT, SOD, vitamin C, HDL and a significant decrease (p<0.05) in the level of urea, MDA, PC, TG, TC, VLDL, TNF-a protein, and the gene expression of TNF-a compared with test without treatment group. Histopathological evidence demonstrated that treatment with T. chebula extract could decrease liver lymphocyte infiltration. Conclusion: The present study suggests that T. chebula fruit extract has protective effects against diazinon-induced oxidative stress.

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Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice

Evidence Based, Complementary and Alternative Medicine 2015;2015:517350. doi: 10.1155/2015/517350. Epub 2015 Jan 26.

We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW) and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP-) induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg) or gallic acid (100 mg/kg) for 5 days before t-BHP (2.5 mM/kg) injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-a, IL-1ß, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines.

[Link to the scientific study]

Acetaminophen-induced Hepato- and Nephrotoxicity and Amelioration by Silymarin and Terminalia chebula in Rats

Toxicology International 2010 Jul;17(2):64-6. doi: 10.4103/0971-6580.72672.

Experimental study was conducted to evaluate the hepato- and renoprotective effect of silymarin and Terminalia chebula against experimentally-induced acetaminophen (APAP) toxicity in rats. Oral administration of APAP @ 500 mg/kg for 1 to 3 days to all the four groups (six rats in each) resulted in significant elevation of serum triglycerides, total cholesterol, blood urea nitrogen, serum creatinine, and aspartate transaminase activity. Post-treatment with silymarin @ 25 mg/kg and T. chebula 125 mg/kg in groups 2 and 3 and their combination to group 4 from day 4 to 14 has significantly reversed the alterations of above said markers and offered better protection. The results of the study enunciated that silymarin and T. chebula exhibit good hepato- and nephro-protection against APAP toxicity.

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