Effect of Yinchenhao Decoction on"Intestinal TPH1-Hepatic HTR2A Axis"in Mice with Metabolic Associated Fatty Liver Disease / 世界科学技术-中医药现代化

ABSTRACT

Objective To explore the mechanism of Yinchenhao Decoction in preventing and treating MAFLD based on"Intestinal TPH1-hepatic HTR2A axis".Methods Twenty-four C57BL/6J mice were arbitrarily splited up into control group,model group and Yinchenhao decoction group,eight in each group.Mice in the Yinchenhao decoction group and model group were fed with high-fat diet.After 12 weeks,the Yinchenhao decoction group was given Yinchenhao decoction by gavage,once a day for 4 consecutive weeks.Histopathological changes were observed by HE staining and oil red O staining.Serum HDL-C,LDL-C,TC,TG,AST,ALT and 5-HT contents,liver TC,TG,DAG,PLC contents were detected.Intestinal TPH1,SERT and liver HTR2A,SREBP-1c,GPAT1,FASN mRNA levels;Intestinal TPH1,SERT and liver HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,PKC-ε,P-AKT,P-mTOR protein expression level were detected.Results In the control group,the hepatocytes were arranged neatly without significant steatosis;In the model group,the hepatocytes were swollen in volume with significant steatosis;Compared with the control group,hepatocyte steatosis was significantly reduced in the Yinchenhao decoction group.Compared with the control group,liver lipid deposition was significantly higher in the model group,and the Yinchenhao decoction group significantly improved liver lipid deposition.Compared with the control group,the liver TG,TC levels in the model group were significantly increased(P<0.05);the serum AST,ALT,HDL-C,LDL-C,TG,TC levels were significantly increased(P<0.05);the serum 5-HT and liver DAG,PLC was significantly increased(P<0.05);the mRNA expression levels of HTR2A,SREBP-1c,GPAT1,FASN in the liver and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly decreased(P<0.05);the protein expression levels of HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,P-AKT,P-mTOR,PKC-ε in the liver were significantly increased,and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly decreased(P<0.05).Compared with the model group,the liver TG,TC levels in Yinchenhao decoction group were significantly decreased(P<0.05);the serum AST,ALT,LDL-C and TG levels were significantly decreased(P<0.05);the serum 5-HT and liver DAG,PLC level was significantly decreased;The mRNA expression levels of HTR2A,SREBP-1c,GPAT1,FASN in the liver and TPH1 in the Intestinal were significantly decreased,SERT in the Intestinal were significantly increased(P<0.05);the protein expression levels of HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,P-AKT,P-mTOR,PKC-ε in the liver were significantly decreased and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly increased(P<0.05).Conclusion Yinchenhao decoction may regulate liver TG synthesis through Intestinal TPH1-hepatic HTR2A axis,thereby inhibiting the occurrence and development of MAFLD.