基于网络药理学、分子对接及实验验证探讨黄芪治疗糖尿病足溃疡的作用机制OA

This study employs network pharmacology and molecular docking method to predict the potential mechanism of Astragalus membranaceus in treating diabetic foot ulcer(DFU),and to conduct experimental verification.Methhod:Active components of Astragalus membranaceus and their potential targets were screened via the TCMSP platform,while DFU-related gene datasets were integrated from disease databases including DisGeNET,CTD,and GeneCards.GO and KEGG pathway enrichment analyses were performed.An"active component-target-signaling pathway"network diagram was constructed by integrating the PPI network to identify major active components and core targets.The AutoDock molecular docking software was employed for docking verification of active components and core targets.Astragalus membranaceus gel was prepared after the docoction,meanwhile a DFU rat model was established by STZ induction combined with dorsal skin excision.The rats were divided into model group and and Astragalus membranaceus group(each for 10),while other 10 rats were elected as the control group.The blank gel plasters was applied to the control and model groups respectively,while the Astragalus membranaceus gel plasters group was applied to the Astragalus membranaceus group.The plasters were changed daily and wound healing status was recorded.The treatment lasted for 14 days.Wound healing was observed on days 0,3,7,and 14 after administration,and the healing rate was calculated.The expression levels of core targets(IL-1β、IL-6、RELA)were quantitatively detected by ELISA.Results:20 active components of Astragalus membranaceus with potential therapeutic effects on DFU were screened,involving 161 common targets.GO analysis revealed 625 biological processes,68 cellular components,and 129 molecular functions were significantly associated with DFU pathogenesis.KEGG pathway enrichment identified 168 key signaling pathways,AGE-RAGE signaling in diabetic complications and IL-17 signaling pathway were involved primarily.Molecular docking demonstrated that the active components of Astragalus membranaceus exhibited high-affinity binding characteristics to IL-1β,IL-6,and RELA.Animal experiments showed the Astragalus membranaceus group exhibited significantly better wound healing status and healing rate compared with the model group,as well as downregulated the expression of IL-6 and RELA.Conclusion:Astragalus membranaceus can promote wound healing in DFU by inhibiting the expression of inflammatory-related factors such as IL-6/RELA,and suppressing inflammatory responses.