“人参-黄芪-葛根”角药修复胰岛形态功能的潜在机制预测及验证  

Prediction and verification of potentialmechanism of “ginseng-astragalus-pueraria”horn medicine in protecting pancreatic islet morphology

作　　者：倪英群 李居一[2] 林逸轩[1] 叶蕾 张喆 方朝晖 NI Ying-qun;LI Ju-yi;LIN Yi-xuan;YE Lei;ZHANG Zhe;FANG Zhao-hui(the First Clinical College,Anhui University of Chinese Medicine,Hefei 230038,China;Dept of Endocrinology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;Key Laboratory of Xin’an Medicine,Ministry of Education,Hefei 230038,China;Institute of Traditional Chinese Medicine for Prevention and Treatment of Diabetes,Anhui Academy of Traditional Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学第一临床医学院,安徽合肥230038 [2]安徽中医药大学第一附属医院内分泌科,安徽合肥230031 [3]新安医学教育部重点实验室,安徽合肥230038 [4]安徽省中医药科学院中医药防治糖尿病研究所,安徽合肥230031

出　　处：《中国药理学通报》2025年第3期574-582,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82274468);新安医学教育部重点实验室开放基金资助项目(No 2022XAYX06);安徽中医药大学临床科研项目(No 2021yfylc07);安徽省高校优秀人才支持计划项目(No gxyqZD2021114);国家公益行业专项课题(No 201507001-11);安徽省中医药传承创新科研项目(No 2024CCCX107)。

摘　　要：目的运用网络药理学预测“人参-黄芪-葛根”角药保护胰岛形态,改善胰岛素抵抗的潜在机制并验证。方法角药活性成分及靶点由TCMSP、TCMIP、BATMAN 3个平台获得。2型糖尿病靶点由TTD、OMIM、disgeNET 3个平台获得。利用STRING数据库和Cytoscape 3.9.1构建PPI网络;进行GO和KEGG分析;POCASA 1.1预测蛋白结合位点,AutoDock Vina1.1.2进行对接,并进行实验验证。结果角药筛选出2021个靶点,其中152个与2型糖尿病密切相关,鉴定出10个关键基因和AGE-RAGE信号通路。分子对接显示,槲皮素与RAGE、INS、PI3K之间具有较好的结合。角药提高胰岛素结合率和分泌指数,降低血清胰岛素水平、胰岛素抵抗指数等,其作用机制可能是角药降低AGE-RAGE的表达,激活PI3K-Akt,抑制NF-κB,降低IL-6、IL-1β和TNF-α的表达。结论“人参-黄芪-葛根”角药通过调节AGE-RAGE/PI3K-Akt/NF-κB信号转导,修复受损胰岛形态,改善胰岛素抵抗。Aim To predict and verify the potential mechanism of the compatibility of“ginseng-astragalus-pueraria”in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TCMSP,TCMIP,and BATMAN.The targets of type 2 diabetes mellitus(T2DM)were obtained from three platforms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cytoscape 3.9.1;GO and KEGG analysis were performed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results“Ginseng-astragalus-pueraria”screened out 2021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were identified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experiments showed that the horn drug increased insulin binding rate and secretion index and reduced serum insulin level and insulin resistance index.These data benefited from“ginseng-astragalus-pueraria”reducing the expression of AGE-RAGE,activating PI3K-Akt,inhibiting NF-κB,and reducing the expression of IL-6,IL-1βand TNF-α.Conclusion The study suggests that“ginseng-astragalus-pueraria”regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resistance.

关 键 词：“人参-黄芪-葛根”角药 胰岛素抵抗 AGE-RAGE PI3K-AKT NF-ΚB 胰岛功能 

分 类 号：R-332[医药卫生] R282.71R322.57R319R347.8R587.1