Hepatoprotective Effect of Qushihuayu Formula on Non-Alcoholic Steatohepatitis Induced by MCD Diet in Rat

Background:NASH is developed from NAFLD and there is no proven pharmaceutical therapy for patients. Traditional Chinese medicine formula of Qushihuayu(QSHY) shows strong advantage because of their various bioactive compounds in curing NAFLD and NASH.Methods:Male Wistar rats with six weeks old received methionine-choline- supplemented diet (MCS) diet for 8 weeks as the blank control. Another 7 rats received MCD diet for 6 weeks first and MCS&MCD (1:1) mixture diet for the last 2 weeks as the model group. QSHY Pre-treatment, low dosage, medium dosage and high dosage groups were received the same diet as the model group. Except for pre-treatment group (1 week in advanced of other groups), all QSHY treatment groups received QSHY formula by gavage every day since the MCD diet started.Results:QSHY formula decreased the serum ALT and AST levels, lipid droplets, inflammation foci, FAS and α-SMA protein expression than MCD diet group. MAPK pathways phospharylation are markedly depressed by QSHY formula. Moreover, QSHY formula enhanced PPAR-γ and p-p65 translocating into nucleus. The administration of QSHY increased hepatic mRNA levels of Transcription Factor 1 alpha (HNF1A), Hepatocyte Nuclear Factor 4 alpha (HNF4A) and Forkhead box protein A3 (FOXA3) which play a pivotal role in Hepatic stellate cell (HSCs) reprogramming.Conclusion:These findings suggest that QSHY formula exerts a hepatoprotective effect against steatosis and fibrosis presumably via depressed MAPK pathways phosphorylation, reinforcement of PPAR-γ and p-p65 translocating into nucleus and enhanced HSCs reprogramming.