Honokiol attenuates Diet-Induced Nonalcoholic Steatohepatitis by regulating macrophage polarization through activating PPARγ.
J Gastroenterol Hepatol. 2017 Jul 2. Epub 2017 Jul 2. PMID: 28670854
BACKGROUND AND AIM: Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. This study aimed to investigate whether honokiol could prevent NASH induced by high cholesterol and high fat (CL) diet in mice and the possible mechanism involved.
METHODS: Mice were fed with CL diet for 12 weeks to establish a NASH model, honokiol (0.02% w/w in diet) was added to evaluate its effect on NASH. Murine peritoneal macrophages, RAW264.7 and ANA-1 cells were used to explore the possible mechanisms of honokiol on macrophage polarization.
RESULTS: Mice developed NASH after fed with CL diet for 12 weeks. Honokiol supplementation alleviated insulin resistance, hepatic steatosis, inflammation and fibrosis induced by CL diet. Immunohistochemistry showed honokiol induced more M2 macrophages in livers compared with CL diet alone. Honokiol decreased M1 marker genes (TNFα, MCP-1), increased M2 marker genes (YM-1, IL-10, IL-4R, IL-13) expression in mice liver compared with CL diet. Moreover, treatment with honokiol lowered ALT and AST in serum and preserved liver from lipid peroxidation, evidenced by lowered hepatic MDA level. Honokiol has antioxidant function, ashonokiol upregulated hepatic GSH and SOD level and downregulated hepatic CYP2E1 protein level. Hepatic PPARγ and its target genes were upregulated by honokiol. Furthermore, honokiol (10 μM) treatment in mouse peritoneal cells, RAW264.7 cells and ANA-1 cells led to M2 macrophage polarization, whereas a PPARγ antagonist, GW9662 abolished this effect of honokiol.
CONCLUSIONS: Honokiol can attenuate CL diet induced NASH and the mechanism in which possibly is polarizing macrophages to M2 phenotype via PPARγ activation.