Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clin...Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development.This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM.Methods:With network pharmacology,we screened substances in JQJT and their possible targets,then constructed the action network and enriched the biological functions and pathways associated with the active components,and identified the potential targets and mechanisms of JQJT in the treatment of T2DM.Based on the network pharmacology data,we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction.Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT,together with 146 potential biological targets.Among these potential targets,74 were associated with treatment of T2DM.A compound-target network of the 43 compounds against T2DM was constructed.Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway.Western blot and quantitative real-time polymerase chain reaction results showed that coptisine,but not epiberberine,significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway.Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis,which may be one of the mechanisms of JQJT in the treatment of T2DM.展开更多
目的:观察降糖三黄片对早期糖尿病肾病大鼠肾组织中糖基化终末产物(Advanced Glycosylation End Products,AGEs)、转化生长因子β1(TGF-β1)的影响,探讨其对肾脏的保护作用。方法:将80只大鼠随机分为正常组11只,造模组69只。采用腹腔内...目的:观察降糖三黄片对早期糖尿病肾病大鼠肾组织中糖基化终末产物(Advanced Glycosylation End Products,AGEs)、转化生长因子β1(TGF-β1)的影响,探讨其对肾脏的保护作用。方法:将80只大鼠随机分为正常组11只,造模组69只。采用腹腔内注射链脲菌素(STZ)复制DN大鼠模型。造模成功的大鼠随机进一步分为模型组、厄贝沙坦组(给药量0.027 g·kg-1·d-1)、降糖三黄片组(给药量0.675 g·kg-1·d-1);正常组、模型组灌服等剂量蒸馏水。8周后处死大鼠。实验结束前收集24 h尿液测定尿蛋白。处死前采血检测血糖、糖化血红蛋白、胰岛素水平。制备肾组织病理切片;测定大鼠肾组织AGEs、TGF-β1含量。结果:造模后各组血糖、糖化血红蛋白、胰岛素及肾组织AGEs、TGF-β1、尿蛋白水平均有升高(P<0.01或P<0.05)。降糖三黄片相对于模型组和厄贝沙坦组,能较好地降低血糖、尿蛋白及AGEs含量(P<0.01);降糖三黄片、厄贝沙坦均能明显抑制DN大鼠肾组织中TGF-β1的表达。病理切片显示模型组肾脏局灶肾小管内见糖原沉积,部分肾小管上皮细胞水肿,部分上皮胞浆透亮,呈空泡样改变;厄贝沙坦组、降糖三黄片组肾小球的基底膜增厚、上皮细胞水肿、毛细血管腔受压的现象得到改善。结论:降糖三黄片能降低血糖水平,增加外周组织对葡萄糖的利用,减少肾组织AGEs的沉积,从而抑制TGF-β1表达,减少尿蛋白排出,减轻肾组织病变进程,效果与厄贝沙坦相近。展开更多
基金the Fundamental Research Funds for the Central Universities(grant number:2021-JYB-XJSJJ-003)the Open Project of State Key Laboratory of Bioactive Substance and Function of Natural Medicines(grant number:GTZK202108)+1 种基金Chinese Society of Toxicology(grant number:CST2021CT101)Discipline Construction Project of Peking Union Medical College(grant number:201920200801).
文摘Background:Jinqi Jiangtang tablets(JQJT)have been approved for the treatment of type 2 diabetes mellitus(T2DM)in China for many years.Exploring the effective substances and mechanisms of JQJT is important for its clinical application and further drug research and development.This study aimed to explore the chemical basis and mechanisms of JQJT in the treatment of T2DM.Methods:With network pharmacology,we screened substances in JQJT and their possible targets,then constructed the action network and enriched the biological functions and pathways associated with the active components,and identified the potential targets and mechanisms of JQJT in the treatment of T2DM.Based on the network pharmacology data,we explored the hypoglycemic mechanisms of coptisine in JQJT through western blot and quantitative real-time polymerase chain reaction.Results:Forty-three compounds with good pharmacokinetic properties were identified in JQJT,together with 146 potential biological targets.Among these potential targets,74 were associated with treatment of T2DM.A compound-target network of the 43 compounds against T2DM was constructed.Biological process and signal pathway enrichment analysis of the network highlighted the FoxO signaling pathway.Western blot and quantitative real-time polymerase chain reaction results showed that coptisine,but not epiberberine,significantly inhibited expression of key genes involved in hepatocyte gluconeogenesis by regulating the FoxO1 signaling pathway.Conclusion:Network pharmacology analysis and cell experiments showed that coptisine regulated glucose homeostasis by inhibiting the FoxO1 signaling pathway and hepatic gluconeogenesis,which may be one of the mechanisms of JQJT in the treatment of T2DM.
