Safety assessment of methanolic extract of Terminalia chebula fruit, Terminalia arjuna bark and its bioactive constituent 7-methyl gallic acid: In vitro and in vivo studies.

Terminalia chebula and Terminalia arjuna were widely used in traditional medicine for the treatment of memory impairment, inflammatory disorders and as an anti-aging agent. However, reports regarding their safety aspects are lacking. Hence, the present study was carried out to investigate the toxicity of methanolic extracts of Terminalia chebula fruit (TCF), Terminalia arjuna bark (TAB) and its bioactive constituent 7- Methyl gallic acid (7MG) under in vitro and in vivo conditions. In vitro toxicity profile of TCF, TAB and 7MG (250-2000 µg/ml) were assessed through cytotoxicity, hemolytic activity, mutagenicity and genotoxicity assays. Results of Ames test, comet assay, MTT and hemolytic assays illustrated that TCF, TAB and 7MG exhibited neither cytotoxic and genotoxic effect in PBMC nor hemolytic activity in RBC and no mutagenic effect in TA 98 and TA 100 up to a limited dose of 2000 µg/ml. Acute and subacute toxicity studies showed no significant change in body weight, behavior, hematology, biochemical parameters, organ weight and histopathology. Over all the results of acute and subacute toxicity studies conclude that oral administration of TCF, TAB and 7MG were observed to be relatively non-toxic and affords practical guidance for selecting safe dose for further clinical trials.

Repeated oral dose toxicity study on hydrolysable tannin rich fraction isolated from fruit pericarps of Terminalia chebula Retz in Wistar albino rats.

Terminalia chebula fruits are one of the richest sources of hydrolysable tannins and it is well known medicinal agent in traditional systems of medicine for treatment of various chronic ailments. In the present study, hydrolysable tannin rich fraction (HTF) was isolated from 80% hydroalcoholic extract of Terminalia chebula fruit pericarps and it was studied for acute and repeated dose oral toxicity in Wistar albino rats. HTF did not show any toxic symptoms or mortality at single dose administration of 5000 mg/kg/p.o followed by observation for 14 days. On repeated dose 28 days oral toxicity study, administration of HTF at 1000 mg/kg showed marked reduction in body weight, food intake and water intake when compared with vehicle control. It was also observed that HTF could increase serum urea, glucose and AST level significantly when compared with vehicle control indicating mild disturbances in liver and kidney functions. On histopathological screening, HTF treatment showed a mild granulomatous inflammation in the liver and all other organs remained normal. It was concluded that following 28 days repeated dose oral administration, HTF caused mild disturbances in liver and kidney function which was indicated by reduced body weight, food and water intake, serum parameters and histological observations.

Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia bellerica (Gaertn.) Roxb. In Spargue-Dawley rats.

Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results showed no signs of toxicity such as general behavior changes, morbidity, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The study of chronic toxicity was determined by oral feeding both female and male rats (10 female, 10 male) daily with the test substance at the dose of 300, 600 and 1,200 mg/kg body weight continuously for 270 days. The examinations of signs of toxicity showed no abnormalities in the test groups compared to the controls. In addition, these rats were analyzed for final body and organ weights, necropsy, as well as hematological, blood chemical and histopathological parameters. Taken together, the water extract from the dried fruits of T. bellerica did not cause acute or chronic toxicities in either female or male rats.

Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents.

BACKGROUND: Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. METHODS: Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. RESULTS: TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. CONCLUSION: The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.