Parthenolide ameliorates metabolic dysfunction-associated steatohepatitis by inhibiting M1 polarization by...

Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory disorder that results in ongoing liver inflammation and injury. During the course of hepatitis, parthenolide (PAR) promotes the recovery of liver function. Using a mouse model of MASH, the present study aimed to assess the effect of PAR on the condition. The MASH mouse model was developed using a high-fat diet combined with high-carbohydrate drinking, and measurements were taken for body weight, liver-to-body mass ratio, non-alcoholic fatty liver disease activity score, and levels of alanine aminotransferase and aspartate aminotransferase. Subsequently, liver injury was detected using hematoxyling and eosin staining, hepatic lipid accumulation was evaluated with oil red O staining, and liver fibrosis was assessed through Masson staining. Macrophage infiltration and M1 polarization were assessed by immunofluorescence staining for F4/80; and lipid metabolic, fibrotic, and pro-inflammatory indicators were detected by RT-qPCR; nuclear factor-κB (NF-κB) signaling pathway was assessed by Western blot. We found that PAR alleviated liver injury, improved lipid metabolism, and reduced fibrosis in MASH mice,. It also lowered macrophage infiltration in the liver, particularly decreasing M1 macrophages and pro-inflammatory cytokines. PAR inhibited the activation of the NF-κB pathway, and the protective effects were attenuated by an NF-κB pathway activators. We conclude that PAR ameliorates liver injury, hepatic lipid metabolism, fibrosis and inflammation in MASH mice, likely by suppressing the NF-κB pathway and thereby inhibiting M1 polarization.