| Objective: Gandi capsule is performed auxiliary therapy for diabetic nephropathy in clinic,but its pharmacological mechanism is still unknown.According to the characteristic of complex compounds and mechanisms of Gandi capsule,we used a network pharmacology strategy to screen of active components and targets to illustrate the pharmacological mechanism of Gandi capsule for diabetic nephropathy.Methods: To facilitate the identification of components,at first,a component database of Gandi capsule and target database of DN were established by ourselves.The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-MS/MS.The potential targets were screened by using Libdockscore in Discovery studio 3.0.Then Pathway analysis and Network analysis were used to enrich the screened targets and pathway.The possible targets were verified by using a surface plasmon resonance(SPR)test and the molecular mechanism focusing these compounds and pathways for treating DN was clarified in HG-induced podocyte cells.Results: Six components in Gandi capsule were identified detected in rat plasma after oral administration according to molecular database and UHPLC-MS/MS.After molecular docking analyses,KEGG and network analysis,four protein targets including HNF4 A,HMGCR,JAK3,and SIRT1,were screened out,and proved as effective binding with baicalin,wogonoside by SPR.And the molecular mechanism was clarified that 5mg/L or 10mg/L baicalin and wogonoside inhibit the effect of high glucose(HG)-induced decreased cell viability and podocin expression,and strengthen the activation of p-AKT,p-PI3 K,and p-AMPK.Conclusions: Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways,which could be the one of the mechanisms of Gandi capsule for treating diabetic nephropathy. |
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