PCHP‑1 A from Polygonatum cyrtonema Hua alleviates APAP‑induced acute liver injury via Nrf2/Keap1 and NF‑κB pathways

Acetaminophen (APAP), a common antipyretic and painkiller, can cause hepatotoxicity and severe liver injury when used in excess, and therapeutic options are quite limited. Polygonatum cyrtonema Hua polysaccharide (PCHP) exhibits good anti-inflammatory and antioxidant properties. Investigating PCHP-1 A protective properties and underlying mechanisms against APAP-induced acute liver injury (ALI) in vivo is the goal of this study. APAP was injected intraperitoneally into mice to establish an ALI model. The protective effects of PCHP-1 A on APAP-induced ALI were systematically analyzed based on indicators such as liver tissue pathological damage, serum biochemistry, liver function enzymes, hepatocyte necrosis, inflammatory cytokines, and oxidative stress. The results indicated that PCHP-1 A pretreatment significantly alleviated APAP-induced ALI. This was manifested by inhibiting liver pathological damage, reducing serum levels of AST, ALT, LDH, ALP, and TBIL, decreasing liver Fe content, and inhibiting hepatocyte apoptosis. Additionally, PCHP-1 A also significantly mitigated APAP-induced liver oxidative stress and inflammatory responses, including inhibiting the levels of proinflammatory cytokines TNF-α, IL-1β and IL-6, decreasing liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, inhibiting liver lipid accumulation, and up-regulating GSH and SOD activity. Notably, PCHP-1 A alleviated APAP-induced hepatic oxidative stress and inflammation, which was associated with modulation of the Keap1/Nrf2 pathway and suppression of the NF-κB pathway. Molecular docking simulations provided molecular-level insights for these effects, suggesting that PCHP-1 A mitigates APAP-induced ALI in vivo through modulation of oxidative stress and inflammatory responses.