摘要
为探究黄芪(Astragalus menbrunucrus)与灵芝(Ganoder malucidum)二种中药对高血糖病(hyperglycemia)的治疗作用机制,本研究利用网络药理学(network pharmacology)分析了黄芪与灵芝对高血糖病的作用靶点和通路,然后运用Autodock预测了活性成分与靶点蛋白的结合能力。结果表明,黄芪与灵芝共有35种有效成分和173个作用靶点,针对高血糖病的靶点有73个。其主要活性成分包括槲皮素、异鼠李素、山奈酚、β-谷甾醇等,通过AKT1、IL6、MAPK1、PPARG、TNF等靶点,作用于胰岛素信号通路、AGE-RAGE信号通路、癌症通路等。分子对接结果显示核心成分与关键靶点具有较好的结合活性。验证试验表明,当黄芪:灵芝质量比为5∶1时,对α-葡萄糖苷酶和α-淀粉酶的抑制效果最佳,分别达到85.81%、78.35%。非酶蛋白糖基化试验(AGEs)显示,同样比例的药物,对AGEs生成的抑制作用最强,为77.38%。二种中药通过多成分、多靶点、多途径协同作用治疗高血糖病,其作用机制与调控胰岛素信号通路、抑制AGE-RAGE信号通路、延缓肠道对葡萄糖的吸收以及改善胰岛素抵抗相关。本研究结果可为黄芪与灵芝复配药物预防治疗高血糖提供理论依据。
To explore the therapeutic mechanisms of Astragalus membranaceus and Ganoderma lucidum in treating hyperglycemia,the target proteins and signaling pathways through which A.menbrunucrus and G.lucidum exert their hypoglycemic effects were elucidated using network pharmacology approaches.Molecular docking was employed to predict the binding affinities between active compounds with target proteins.A.menbrunucrus and G.lucidum possessed 35 effective constituents and 173 correlated targets,among which 73 were specific to hyperglycemia.The main active components of A.menbrunucrus and G.lucidum included quercetin,isorhamnetin,kaempferol,β-sitosterol,and etc.They acted on insulin signaling pathway,AGERAGE signaling pathway,and cancer pathway,with corresponding targets including AKT1,IL6,MAPK1,PPARG,and TNF.Molecular docking indicated that the core bioactive components showed strong binding affinities with these key target proteins.Enzyme activity assays revealed a 5∶1 ratio(m/m)of A.menbrunucrus to G.lucidum exhibited maximum inhibitory effects onα-glucosidase andα-amylase with 85.81%and 78.35%respectively.Non-enzyme protein glycosylation experiments demonstrated that(AM-GL(5∶1))reduced advanced glycation end products(AGEs)generation by 77.38%.These two traditional Chinese medicines synergistically treated hyperglycemia through a multi-component,multi-target and multipathway mechanism,involving the regulation of insulin signaling pathway,inhibition of AGE-RAGE signaling pathway,retardation of intestinal glucose absorption and improvement of insulin resistance.The results of this study provide theoretical basis for the clinical application of of A.membranaceus and G.lucidum in prevention and treatment of hyperglycemia.
作者
赵可
艾对元
靳亚弟
段欢欢
贠建民
ZHAO Ke;AI Duiyuan;JIN Yadi;DUAN Huanhuan;YUN Jianmin(College of Food Science and Engineering,Gansu Agricultural University,Lanzhou,Gansu 730070)
出处
《核农学报》
北大核心
2026年第1期66-80,共15页
Journal of Nuclear Agricultural Sciences
基金
甘肃省强科技补助资金项目(NXKJ2023-02)。
关键词
黄芪
灵芝
高血糖
网络药理学
AGE-RAGE信号通路
Astragalus menbrunucrus
Ganoder malucidum
hyperglycemia
network pharmacology
AGE-RAGE signaling pathway
