Evaluating the hepatotoxicity and nephrotoxicity of herbal medicine on swiss albino mice: an in-vivo, in-vitro and in-silico insights

Herbal medicines, including traditional formulations such as Carmina, a polyherbal remedy widely prescribed for gastric ailments, require rigorous safety validation to support their clinical use. Here, we evaluate the hepato-renal toxicity of Carmina following oral administration in Swiss albino mice over a 14-day period. Carmina was administered at doses of 0.5 and 2.5 mL/kg body weight/day. Paracetamol (500 mg/kg, single dose on day 13) was used as a hepatotoxic and nephrotoxic positive control. Maxpro (0.7 mg/kg/day), a standard allopathic gastric remedy, was used as a therapeutic comparator. Carmina treatment did not significantly alter body or organ weights, nor organ indexing ratios. Biochemical assays revealed a significant reduction (p < 0.05) in alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides, blood urea nitrogen (BUN), and urea levels compared to saline controls, while alkaline phosphatase (ALP), bilirubin, and malondialdehyde (MDA) levels were slightly elevated but not statistically significant. Notably, increased levels of albumin (ALB), reduced glutathione (GSH), and catalase (CAT) were observed in both liver and kidney tissues, suggesting enhanced antioxidant capacity. Histopathological evaluation confirmed normal cellular architecture in hepatic and renal tissues. 3D-QSAR model validation indicated acceptable predictive power (r² > 0.6; q² > 0.5) for all plant constituents except Zingiber officinale. While these findings indicate no evidence of acute hepatorenal toxicity of Carmina in this 14-day subacute study, further molecular investigations (including chronic toxicity studies and western blotting) are required to confirm its long-term safety and mechanistic basis.