世界中医药2025，Vol.20Issue(13)：2239-2248,10.DOI:10.3969/j.issn.1673-7202.2025.13.003
紫草素治疗糖尿病足溃疡的疗效及基于网络药理学的作用机制
Therapeutic Effects and Mechanisms of Shikonin on Diabetic Foot Ulcers in Mice Based on Network Pharmacology
摘要
Abstract
Objective:To investigate the mechanism of action of shikonin in treating diabetic foot ulcers(DFU)using network pharmacology,molecular docking,and animal experiments.Methods:Relevant targets of shikonin and DFU were obtained from da-tabases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SwissTarget-Prediction,and GeneCards.The intersecting targets were used to construct a protein-protein interaction(PPI)network,followed by Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KE GG)pathway enrichment analysis.Molecular docking was performed to assess the binding affinity between shikonin and core targets.Ultra-performance liquid chroma-tography-mass spectrometry(UPLC-MS)was used to identify shikonin in the extract.A DFU mouse model was established to verify the expression levels of key proteins.Results:Network pharmacology identified hypoxia-inducible factor 1 alpha(HIF1A),signal transducer and activator of transcription 3(STAT3),nuclear factor kappa B1(NF-κB1),histone deacetylase 2(HDAC2),and vas-cular endothelial growth factor receptor 2(KDR)as core targets of shikonin in DFU treatment.Molecular docking showed the best binding affinity between shikonin and HIF1A,with the HIF-1 signaling pathway being a potential mechanism for shikonin's thera-peutic effect.UPLC-MS results confirmed a high match between shikonin and the reference compound.Animal experiments demon-strated that shikonin treatment downregulated HIF1A expression,inhibited secretion of tumor necrosis factor-alpha(TNF-α)and in-terleukin-8(IL-8),promoted expression of interleukin-10(IL-10)and vascular endothelial growth factor(VEGF),thereby reducing inflammation and promoting angiogenesis.The high concentration group showed the best effect.Conclusion:Shikonin improves the hypoxic environment of DFU by inhibiting the HIF-1 signaling pathway,alleviates inflammatory responses,promotes angiogenesis,and accelerates DFU healing.关键词
紫草素/糖尿病足溃疡/网络药理学/分子对接/缺氧/炎症反应/血管新生Key words
Shikonin/Diabetic foot ulcer/Network pharmacology/Molecular docking/Oxygen-poor/Inflammatory response/Angio-genesis分类
医药卫生引用本文复制引用
袁美杰,朱旭莹,史宏硕,赵卓,樊炜静,胡啸明,孙健,游洋,柳国斌..紫草素治疗糖尿病足溃疡的疗效及基于网络药理学的作用机制[J].世界中医药,2025,20(13):2239-2248,10.基金项目
国家自然科学基金面上项目(82274528) （82274528）
上海中医药大学科技发展基金(23KFL107) （23KFL107）
