Parthenolide plays a protective role in the liver of mice with metabolic dysfunction-associated fatty liver disease through the activation of the HIPPO pathway

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a serious threat to human health. Parthenolide (PAR) displays several important pharmacological activities, including the promotion of liver function recovery during hepatitis. The aim of the present study was to assess the effect of PAR on MAFLD in a mouse model. Body weight, liver to body weight ratios, histological score, alanine transaminase, aspartate transaminase, total cholesterol and triglyceride levels were determined to evaluate liver injury. Liver hydroxyproline concentrations were also assessed. The expression levels of lipid metabolism-related genes (sterol regulatory element binding protein-1c, fatty acid synthase, acetyl CoA carboxylase 1, stearoyl CoA desaturase 1 and carbohydrate response element-binding protein, peroxisome proliferator-activated receptor α, carnitine palmitoyl transferase 1α and acyl-CoA dehydrogenase short chain), liver fibrosis-associated genes (α-smooth muscle actin, tissue inhibitor of metalloproteinase 1 and TGF-β1), pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and oxidative stress-associated enzymes (malondialdehyde, superoxide dismutase and glutathione peroxidase) were measured in mice with MAFLD. The expression levels of genes associated with the HIPPO pathway were also measured. In vivo experiments using a specific inhibitor of HIPPO signalling were performed to verify the role of this pathway in the effects of PAR. PAR exerted beneficial effects on liver injury, lipid metabolism, fibrosis, inflammation and oxidative stress in mice with MAFLD, which was mediated by activation of the HIPPO pathway.