Shenling Baizhu powder alleviates non-alcoholic steatohepatitis by reducing PPARα-mediated NLRP3 inflammasome activation

Abstract

Introduction Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease characterized by varying degrees of inflammation, hepatic steatosis, liver cell damage and fibrosis, which can seriously harm people’s health. Shenling Baizhu (SL) powder exhibits a strong capacity to modulate cellular mechanisms, thereby demonstrating exceptional potential in addressing inflammatory and oxidative stress-related pathologies. However, the exact mechanism of SL in NASH has not been fully elucidated. We aimed to explore the therapeutic effect and potential mechanism of SL in NASH mice. Methods We fed mice the methionine-choline deficiency (MCD) diet to construct a model of NASH. The efficacy of SL in regulating the progression of NASH was evaluated by biochemical and histopathological analyses. The effects of SL on oxidative stress and inflammatory cytokines were examined. Transcriptomic analysis was performed to further explore the potential molecular mechanisms regulated by SL. Finally, the expression of key proteins was verified by Western blotting. Results The pathological phenotype of NASH was successfully established in mice. SL intervention demonstrated significant therapeutic benefits in reducing hepatic lipid accumulation, alleviating liver fibrosis, and decreasing inflammatory responses. Additionally, SL intervention was shown to ameliorate ER stress by attenuating the unfolded protein response (UPR). Gene expression profiling coupled with pathway analysis revealed that SL exerted its effects through the modulation of critical signalling pathways, including the PPAR signalling axis. Additionally, SL inhibited NLRP3 inflammasome activation and reduced the expression of downstream inflammatory cytokines in the liver. Discussion The findings indicate that SL mitigates NASH by activating the PPAR pathway and suppressing the ER stress-triggered UPR, thereby inhibiting NLRP3 inflammasome activation. These results highlight the therapeutic potential of SL for NASH management.