Abstract
BackgroundNon-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD) for which there is yet any standard pharmacotherapy. Traditional Chinese medicine formula such as Qushihuayu (QSHY) composing of multiple bioactive compounds has been used to treat NAFLD and NASH and shows beneficial effects over single compound treatment. This study aimed to investigate the mechanism of hepatoprotective effect of QSHY formula using a rat model.MethodsSix-weeks old male Wistar rats were given methionine/choline supplemented (MCS) diet for 8 weeks and used as the blank control. Another 7 rats, which received methionine/choline deficient (MCD) diet in the first 6 weeks and a MCS&MCD (1:1) mixture diet in the last 2 weeks, were used as the model group. The groups of QSHY pre-treatment, low dosage, medium dosage and high dosage were given 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.ResultsIn the MCD diet group, the 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 were markedly depressed by the 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.ConclusionThese 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.
Highlights
Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD) for which there is yet any standard pharmacotherapy
Bodyweight, ratio of liver weight to bodyweight, Serum level of TC, TG, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) To investigate the effect of QSHY formula on body composition and lipid metabolism, bodyweight, liver weight and serum level of TC, TG, ALT and AST were measured
At week 6, the serum level of AST decreased significantly in all of the 3 treatment groups when compared with the methionine/choline deficient (MCD) diet group
Summary
Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD) for which there is yet any standard pharmacotherapy. Traditional Chinese medicine formula such as Qushihuayu (QSHY) composing of multiple bioactive compounds has been used to treat NAFLD and NASH and shows beneficial effects over single compound treatment. Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease with a high prevalence worldwide that continues to grow [1]. NAFLD represents a spectrum of histological abnormalities that ranges from simple fatty liver to the more advanced form of. Most of NAFLD patients have simple steatosis, 7–30% of the cases developed chronic hepatic inflammation associated with cirrhosis, portal hypertension and hepatocellular carcinoma. The causes of progression from NAFLD to NASH remain unclear
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