Volvariella volvacea polysaccharides alleviate acute liver injury by modulating Nrf2/NF-κB pathway in a dual manner

Volvariella volvacea is an edible and medicinal fungus; however, its hepatoprotective effects have not been reported. In this study, we evaluated the hepatoprotective effects of V. volvacea polysaccharides (SMP) by constructing a cellular model of H₂O₂-induced oxidative damage and an animal model of tetrachloromethane (CCl₄)-induced acute liver injury in mice. Moreover, we used ML385, a specific Nrf2 blocker, to explore how SMP might regulate the Nrf2 signaling pathway. SMP is a primarily glucose-based polysaccharide with antioxidant capacities. In vitro analyses revealed that the administration of SMP significantly activated Nrf2, upregulated the expression of HO-1 and NQO1, enhanced SOD and CAT enzyme activities, and attenuated reactive oxygen species in H₂O₂-injured hepatocytes. In vivo, SMP reduced the serum levels of ALT, TNF-α, IL-6, and MDA while increasing the activity of hepatic SOD and ameliorating CCl₄-induced histopathology. Our findings revealed that SMP acts via a dual mechanism involving Nrf2-mediated antioxidant pathway activation coupled with NF-κB inflammatory signaling suppression. Collectively, our findings provide a pharmacological foundation for the therapeutic application of SMP in hepatoprotection.