Prediction of the Mechanism of Action of Weifuchun Capsules in the Treatment of Diabetic Gastroparesis and Investigation of the Material Basis of Pharmacodynamic Effect

OBJECTIVE  To preliminarily elucidate the potential mechanism and material basis of Weifuchun capsules in the treatment of diabetic gastroparesis(DGP).

METHODS  The literature was searched to obtain WeiFuchun capsules entry components, action targets, and DGP-related targets, and to construct a medicinal flavour-component-target network diagram and a protein-protein interaction(PPI) network diagram. GO enrichment and KEGG pathway analyses were performed on the intersecting targets. An animal model of DGP was constructed to test the indicators related to gastric motility, evaluate the efficacy of WeiFuchun capsules, and validate the key targets and pathways predicted by network pharmacology using Western blotting. Potential key compounds were analysed based on topological networks and validated by molecular docking.

RESULTS  Based on the literature search, 77 blood components of Weifuchun capsules were obtained, and 663 blood component targets were predicted by TCMSP search and SwissTargetPrediction. There were 76 targets that intersect with DGP, and PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), insulin(INS), interleukin-1 Beta(IL-1β), albumin(ALB), interleukin-2(IL-2), rostaglandin-endoperoxide synthase 2(PTGS2), etc. were the core targets. The GO enrichment results showed that 1503 types of biological processes, 43 types of cellular components, and 98 types of molecular functions were involved. KEGG enrichment results showed that 107 pathways were involved, including diabetic complications AGR receptor signaling pathway, calcium ion signaling pathway, C-type lectin receptor signaling pathway, fluid shear stress and atherosclerosis, blood lipids and atherosclerosis might be the core pathway for the effect of stomach rejuvenation. Compared with the model group, the body weight of rats in the administration group increased significantly; compared with the model group, the gastric emptying rate, intestinal propulsion rate, motilin, gastrin of rats in each administration group were significantly increased(P<0.05). Western blotting were conducted to validate the selected network pharmacologically predicted action proteins, and it was found that the relative expression levels of INS, NOS3, and MAPK were significantly up-regulated, and the relative expression level of IL-1β was significantly down-regulated in the rats of the WeiFuchun apsules intervention group. The basic potential active substances include bluecalyxin A, bluecalyxine B, Melissoidesin U, isorhamnetin, etc., which were well connected with the core targets.

CONCLUSION  Weifuxun capsules can regulate diabetic complications AGR receptor and other signaling pathways by acting on INS, MAPK, TNF, NOS3, IL-1β and other targets, thereby improving gastrointestinal motility, regulating glucose and lipid metabolism disorders, and reducing diabetes complications in DGP model rats. Microvascular damage and other effects, its potential pharmacological material basis may be cyanacaldin A, cyanacaldin B, Melissoidesin U, isorhamnetin, etc.