OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential ...OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.展开更多
目的探讨糖复康方对KK-Ay小鼠降糖的疗效及其与肠道菌群之间复杂的生物网络关系。方法将8周龄SPF级24只KK-Ay自发糖尿病模型小鼠随机分为模型组、糖复康方高剂量组、糖复康方等剂量组、二甲双胍组4组,各6只;6只C57BL/6J小鼠作为正常对...目的探讨糖复康方对KK-Ay小鼠降糖的疗效及其与肠道菌群之间复杂的生物网络关系。方法将8周龄SPF级24只KK-Ay自发糖尿病模型小鼠随机分为模型组、糖复康方高剂量组、糖复康方等剂量组、二甲双胍组4组,各6只;6只C57BL/6J小鼠作为正常对照组。正常对照组及模型组每日给予生理盐水灌胃,糖复康方高剂量组、等剂量组分别给予糖复康方6.4、3.2 g/(kg·d)灌胃,二甲双胍组给予二甲双胍250 mg/(kg·d)灌胃。均干预1个月后取材,同时检测小鼠血糖,光学显微镜下观察骨骼肌细胞病变程度,采用16S r DNA测序法分析小鼠肠道菌群的结构。结果糖复康方可有效降低小鼠血糖,减轻骨骼肌炎症浸润及萎缩坏死,增加小鼠的肠道菌群的多样性,拟杆菌相对丰度增加,而厚壁菌门的相对丰度降低。结论糖复康方对KK-Ay小鼠具有良好的降糖作用,其治疗作用可能与调节肠道菌群结构相关。展开更多
基金Tsinghua Precision Medicine Foundation:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Patients with Qi and Yin Deficiency Syndrome by Regulating the Intestinal Flora Mediated Branched-chain Amino Acids-Phosphatidylinositide 3-Kinases-Protein Kinase B Signaling Pathway(grant number 10001020105)National Natural Science Foundation of China:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Mellitus by Regulating the Intestinal Flora Mediated Adiponectin-adenosine 5-Monophosphate-activated Protein Kinase-branched-chain Amino Acids Signaling Pathway(grant number 82104812)。
文摘OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.
文摘目的探讨糖复康方对KK-Ay小鼠降糖的疗效及其与肠道菌群之间复杂的生物网络关系。方法将8周龄SPF级24只KK-Ay自发糖尿病模型小鼠随机分为模型组、糖复康方高剂量组、糖复康方等剂量组、二甲双胍组4组,各6只;6只C57BL/6J小鼠作为正常对照组。正常对照组及模型组每日给予生理盐水灌胃,糖复康方高剂量组、等剂量组分别给予糖复康方6.4、3.2 g/(kg·d)灌胃,二甲双胍组给予二甲双胍250 mg/(kg·d)灌胃。均干预1个月后取材,同时检测小鼠血糖,光学显微镜下观察骨骼肌细胞病变程度,采用16S r DNA测序法分析小鼠肠道菌群的结构。结果糖复康方可有效降低小鼠血糖,减轻骨骼肌炎症浸润及萎缩坏死,增加小鼠的肠道菌群的多样性,拟杆菌相对丰度增加,而厚壁菌门的相对丰度降低。结论糖复康方对KK-Ay小鼠具有良好的降糖作用,其治疗作用可能与调节肠道菌群结构相关。
