Study on the mechanism of Jinlong Bushen Mixture against metabolic syndrome based on network pharmacology
Objective To investigate the effects and mechanism of Jinlong Bushen Mixture against lipid metabolism disorders induced by high-sugar and high-fat diet in rats with metabolic syndrome by combining network pharmacology and experimental validation.Methods TCMSP and related literature were retrieved to obtain the active components and targets of wolfberry,golden cherry,longan meat,jujube,gynostemma,rosmarinus officinalis,and motherwort in Jinlong Bushen Mixture,and GeneCards online database was retrieved to obtain metabolic syndrome-related targets.Venny 2.1.0 was used to obtain the intersection targets of Jinlong Bushen Mixture and metabolic syndrome,and STRING online STRING online database was used to construct the PPI network of intersecting targets.Core targets in the top 50 degree values were screened using the Cyto NCA plugin in Cytoscape 3.9.0.The DAVID Bioinformatics Resources 6.8 online analysis platform was used for GO functional enrichment and KEGG pathway enrichment analysis.Metabolic syndrome rat model was established using high sugar,high salt,and high fat feed for 20 weeks.The successfully modeling rats were divided into model groups,positive control group and Jinlong Bushen Mixture group according to random number table,and a blank control group was also set up,with 8 rats in each group.Jinlong Bushen Mixture group was gavaged with Jinlong Bushen Mixture 1.8 ml/kg,a positive control group was gavaged with Metformin 90 mg/kg,and the blank and model groups were gavaged with an equal volume of saline,1 time/d,for 4 weeks.The changes in body weight,abdominal circumference,and fasting blood glucose in rats were observed.The blood lipid level in rats was detected.The pathological changes of liver tissues were detected by HE staining.The levels of ATP,IL-1β,and IL-6 in liver tissues were determined by ELISA.The mRNA expression of liver kinase B1(LKB1),AMPK,Akt1,carnitine palmitoyltransferase 1A(CPT1A),and downregulated lactate dehydrogenase A(LDH-A)in liver tissue were detected by qRT-PCR.Western blot was used to determine the expression of p-LKB1,LKB1,p-AMPK,AMPK,p-Akt1,and Akt1 in liver tissue were detected by Western blotting.Results A total of 141 main active components,841 active targets,18 763 metabolic syndrome targets,and 820 drug-disease intersection targets of Jinlong Bushen Mixture were obtained.The KEGG pathway enrichment analysis yielded 173 entries,including mainly the PI3K-Akt,and HIF-1 signalling pathway.The experimental results showed that the weight,fasting blood glucose,and lipid levels of rats in the Jinlong Bushen mixture group decreased,and the disorder of liver glucose and lipid metabolism in rats improved;the levels of ATP,IL-1β and IL-6 decreased(P＜0.05);The mRNA expression of LKB1,AMPK,Akt1,and CPT1A in liver tissue increased(P＜0.05),while LDH-A mRNA expression decreased(P＜0.05).The p-LKB1/LKB1,p-AMPK/AMPK,and p-Akt1/Akt1 ratio increased(P＜0.05).Conclusion Jinlong Bushen Mixture may restore lipid metabolism disorders in the metabolic syndrome through multiple targets and pathways.Its mechanism may exert pharmacological effects through the LKB1/AMPK/Akt signaling pathway.
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