Study on the Efficacy of Jianpi Qushi Decoction in the Treatment of Nonalcoholic Fatty Liver in Rats
[Objective]The purpose of this experiment was to elucidate the pharmacological efficacy and molecular mechanism of Jianpi Qushi decoction(JQD)in the treatment of non-alcoholic fatty liver disease(NAFLD)in rats.[Method]After the rat NAFLD model was established by feeding high-fat diet,the rats were randomly divided into model,orlistat(32.4 mg/kg),JQD low(0.35 g/kg)and high(0.70 g/kg)dose groups,and control group was set up,with 6 rats in each group.Rats in orlistat and JQD different dose groups were given intragastric administration,1 mL/rat,once a day for 7 weeks,and the rats in control and model groups were given intragastric administration of equal dose of normal saline.After the experiment,the blood and liver tissues of rats were collected.Serum lipid levels of rats were determined by ELISA,including total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C).The liver index of rats was measured and the liver antioxidant indexes,including glutathione(GSH),superoxide dismutase(SOD),catalase(CAT)and malondialdehyde(MDA)were detected.HE staining and oil red O staining were used to observe the morphological structure of liver.The active ingredients and key targets of JQD for NAFLD were analyzed using drug and disease target database.The"drug-ingredient-target"network diagram was constructed by Cytoscape 3.7.2 software.The effects of main active ingredients of JQD and key targets were verified by molecular docking and Real-time quantitative PCR.[Result]Compared with control group,the contents of TC,TG and LDL-C in serum,MDA content in liver and liver index in model group were significantly or extremely significantly increased(P＜0.05 or P＜0.01),HDL-C content in serum,GSH content,SOD and CAT activities in liver were significantly or extremely significantly decreased(P＜0.05 or P＜0.01).Compared with model group,the contents of TC and TG in serum,MDA content in liver and liver index of rats in JQD low and high dose groups were significantly decreased(P＜0.05),and the activities of SOD and CAT,and GSH content in liver were significantly increased(P＜0.05).The results of HE staining and oil red O staining showed that the liver cells of control group were normal and the liver cords were neat.In the model group,the liver showed obvious adipose deformation,hepatocyte atrophy,vacuoles of different sizes,and disordered liver cord morphology.The number of liver vacuoles decreased significantly in JQD low and high dose groups,and hepatic cords were clearly visible.A total of 35 active ingredients of JQD and 1 890 disease targets of NAFLD were identified by network pharmacology.The results of network topology analysis showed that the core active ingredients of JQD in the treatment of NAFLD were kaempferol,isorhamnetin and quercetin,and the core therapeutic targets were tumor necrosis factor(TNF),peroxisome proliferating-activated receptor y(PPARG)and vascular endothelial growth factor A(VEGFA).Molecular docking results showed that the binding energies of core active ingredients and key targets were less than-5.0 kJ/mol,and they had good binding activity with each other.Real-time quantitative PCR results showed that compared with model group,the expressions of TNF and PPARG genes in liver of JQD low and high dose groups were extremely significantly decreased(P＜0.01).The expression of VEGFA gene in JQD high dose group was extremely significantly decreased(P＜0.01).[Conclusion]JQD had shown good therapeutic effect on NAFLD,and the mechanism might be related to reducing blood lipid level and increasing antioxidant enzyme activity in liver.
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