The Preventive Effects Of Honokiol And Baicalin On Nonalcoholic Steatohepatitis And The Mechanisms Involved

Background and aim: Nonalcoholic steatohepatitis may develop into hepatic cirrhosis.The step of simple fatty liver to NASH plays a key role for the progression of NAFLD.To date,there is no medicine working well for NASH.Therefore,looking for drugs to treat NASH is imminent.Honokiol(HNK)is a partial agonist of PPAR? with the anti-inflammatory effects on macrophages.Whether HNK inhibits NASH development and its mechanism in it is not clear so far.Baicalin(BC)is a traditional Chinese medicine used to protect liver.While whether BC can reduce NASH is not conclusive.This study aimed to investigate whether HNK or BC could prevent NASH and the possible mechanism involved.The study is divided into two parts.Part I: Explore the effects of HNK on NASH and the mechanisms involvedMethods: Thirty C57 BL male mice were divided into three groups: the normal diet group;the high fat and high cholesterol diet group(CL group);the CL diet with the supplement of HNK(0.02% w/w in diet).After 12 weeks feeding,the HOMA-IR,liver histology,ALT and AST were evaluated.We also evaluate the polarization state of Kupffer cells.RAW264.7 cells,ANA-1 cells and mouse peritoneal macrophages were used to explore the role of HNK on macrophages and the possible mechanism involved.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.HNK induced more M2 macrophages and less M1 macrophages in liver compared with CL diet alone.HNK improved liver function,increased liver SOD activity,GSH content,down-regulated liver MDA.HNK(10?M)treatment polarized mouse peritoneal macrophages,RAW264.7 cells and ANA-1 cells to M2 subtype,whereas a PPAR? 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 PPAR? activation.Part II: Effects of baicalin on NASHMethods: Thirty C57 BL male mice were randomly divided into three groups: normal control group(normal diet),NASH model group(high fat and high cholesterol diet)and BC group(0.5% w/w BC).12 weeks later,the liver histology,liver function,and oxidative stress were evaluated.In vitro experiments using RAW264.7 cells,bone marrow-derived macrophages(BMMs)to explore the role of BC on macrophages.Results: High fat and high cholesterol diet induced NASH after 12 weeks feeding.Compared with NASH mice,steatosis,inflammation and fibrosis were reduced in the liver of the BC group.BC improves liver function and improves oxidative stress in the liver.In vitro experiments showed that BC(10 ?g / ml)treatment of RAW264.7 cells and BMMS could reduce the cellular inflammatory response.Conclusion: BC can reduce dietary induction in NASH,which may be associated with BC antiinflammatory and anti-oxidative effects.