Aims: Nonalcoholic steatohepatitis is one of the most serious health problems in the world and was considered the main cause of cirrhosis. Apoptosis and necroptosis signaling pathways are highly implicated in NASH, so this study aimed to investigate the underlying molecular mechanism for the role of Kaempferol and pioglitazone either alone or their combination in modulating NASH.
Methods: forty C57BL/6J male mice were divided into five groups: Control group: mice received a standard chow diet and receiving vehicle, NASH group: mice were allowed off the NASH protocol for 25 days, KP group: Mice were maintained on NASH protocol for 25 days and were given (40 mg/kg) kaempferol daily via oral gavage, PIO group: mice were maintained on NASH protocol for 25 days parallel with Pioglitazone (50 mg/kg), daily via oral gavage, KP+PIO group: mice have received NASH protocol parallel with KP and PIO co-administration with the same dose.
Results: levels of glucose, insulin, HOMA IR, LDL-C, total cholesterol and triglycerides concentrations were significantly reduced in KP, PIO, and KP+PIO treated groups, while HDL-C was significantly raised compared to the NASH group. Otherwise, gene expression of liver AMPK was significantly increased and PPAR, SREBP, pMLKL were significantly decreased in the other three treated groups. Protein expression of caspase 8 and RIPK3 showed a significant decrease and immunohistochemical expression of NF-κB, TNF-α and IL-6 in KP, PIO, and KP+PIO relative to NASH group.
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