Effects of Gegen Qinlian Decoction on PERK-eIF2α pathway in rats with nonalcoholic steatohepatitis based on endoplasmic reticulum stress
OBJECTIVE To evaluate the therapeutic effect of Gegen Qinlian Decoction(GQD)on rat model with Nonalco-holic Fatty Liver Disease(NAFLD)and its effect on PERK-eIF2α pathway,investigating the mechanism of GQD's action on Endoplasmic Reticulum Stress(ERS).METHODS The non-alcoholic fatty liver rat model was induced using high-fat and high-fructose diet.A control group,a model group,a positive group and different dosage groups were set up.Physical appear-ance,ALT,AST,TG,TC,insulin resistance index and insulin sensitivity index were measured to assess the efficacy of GQD on NAFLD rats.CO-IP,Western blot and RT-qPCR experiments were conducted to investigate the impact of GQD on the PERK-eIF2a pathway in NAFLD rats,and evaluate its role in the endoplasmic reticulum stress response.RESULTS Each GQD dosage could alleviate abnormal body weight decline in NAFLD rats,and significantly reduce the ALT,AST,TG,TC levels.It mitigated the damage of liver function and lipid metabolism disorders caused by NAFLD,increased the insulin sensitiv-ity index,and reduced the insulin resistance index,with therapeutic effects showing dose-dependency.CO-IP,Western blot and RT-qPCR test results indicated that,after GQD treatment,there was a significant increase in the amount of GRP78 & PERK complex in the liver tissues,suppression of eIF2α,P-eIF2α,ATF4,CHOP and other proteins and mRNA,and an increase in GADD34 protein and mRNA expression,with all effects exhibiting dose-dependency.CONCLUSION Gegen Qinlian Decoc-tion can alleviate the endoplasmic reticulum stress response in the liver of NAFLD rats by regulating the PERK-eIF2α-ATF4 sig-naling pathway.
Gegen Qinlian Decoctionnon-alcoholic fatty liverendoplasmic reticulum stressGRP78PERK
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