Kadsura coccinea Roots Ameliorated Alcohol-Induced Liver Injury by Modulating Oxidative Stress Through the Regulation of the Nrf2/MAPK Signaling Pathway

root (KCR) against alcohol-induced liver injury (ALI) utilizing a murine experimental system. Male Balb/c mice were administered alcohol intragastrically in a stepwise manner over 8 weeks to establish the ALI model. Experimental outcomes demonstrated that KCR administration substantially improved hepatic functional status, evidenced by marked reductions in circulating hepatic enzymes, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT). KCR also increased glutathione (GSH) activity, reduced malondialdehyde (MDA) levels in the liver, and exerted antioxidant effects by boosting the expression of enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase 4 (GPX4). Additionally, metabolomic and transcriptomic analyses identified metabolites and pathways closely linked to oxidative stress, including Glutathione metabolism and the MAPK signaling pathway. Further mechanistic studies revealed that KCR could decrease the phosphorylation of p38, JNK, and ERK, while increasing the expression of Nrf2, HO-1, and NQO1. In conclusion, KCR alleviates ALI by modulating the MAPK/Nrf2 pathway, restoring redox homeostasis, enhancing antioxidant defenses, and improving metabolic disorders.