A traditional medicinal food Arum rupicola (Kardeh) ameliorates thioacetamide-induced hepatotoxicity in animal model: Role of PCNA/Bax, oxidative stress, and inflammatory cytokines

Nutraceuticals are major contributors to human health because of their modulatory effects on various physiological and pathological processes. Arum rupicola (Kardeh) is a traditional medicinal food used for many gastrointestinal and enzymatic disorders. The present study evaluates the acute toxicity and hepatoprotective effects of methanolic extracts of Arum rupicola (MEAR) in rat with thioacetamide (TAA)-induced liver injury in rat. Thirty Sprague-Dawley rats were divided into five groups: Group A, normal control, and group B, TAA control groups were treated orally with 10% tween 20; group C reference rat received daily of 50 mg/kg silymarin drug; Groups D and E rat received daily doses of 250 mg/kg and 500 mg/kg MEAR, respectively. In addition, group B-E received three injections of 200 mg/kg TAA weekly for 60 days. The safety evaluation of MEAR revealed nontoxic effects at 2,000 and 5,000 mg/kg dosage in rat. TAA inoculation provoked significant hepatotoxic alterations indicated by increased hepatocyte proliferation, endothelial tissue injury, ambiguous nucleus, and elevated cytoplasmic vacuoles. TAA treatment initiated increased inflammatory response and necrosis process in different areas of hepatic tissues. Meanwhile, MEAR treatment showed significant prophylaxis against TAA-induced hepatotoxicity, supported by its suppressing actions on oxidative stress, and apoptotic and inflammatory mediators. MEAR treatment significantly down-regulated proliferating cell nuclear antigen (PCNA) in both liver and spleen parenchymal tissues, lowered pro-apoptotic Bcl-2-associated X (Bax) proteins, reduced inflammatory and redox mediators, lowered transforming growth factor-beta tissue expression and malondialdehyde content, while, increased antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). The outcomes provided significant hepatoprotective potential of MEAR mediated by its modulatory effects on several cellular pathways, making it a viable source of a potent pharmaceutical discovery.