目的筛选人参、黄连药对主要活性成分,预测其活性成分的作用靶点,建立药物—活性成分—作用靶点网络,探讨人参、黄连药对治疗2型糖尿病(diabetes mellitus type 2,T2DM)的作用机制。方法使用TCMID、TCMSP平台筛选人参、黄连药对化学成分...目的筛选人参、黄连药对主要活性成分,预测其活性成分的作用靶点,建立药物—活性成分—作用靶点网络,探讨人参、黄连药对治疗2型糖尿病(diabetes mellitus type 2,T2DM)的作用机制。方法使用TCMID、TCMSP平台筛选人参、黄连药对化学成分,并应用STITCH及DrugBank数据库检索活性成分靶点。应用TTD、DrugBank、GAD和DisGeNET数据库,筛选T2DM相关靶点。采用Cytoscape软件构建药对活性成分—作用靶点网络,通过David数据库对靶点进行生物学功能及通路富集分析。结果筛选得到人参、黄连药对潜在活性成分46个,人参相关靶点144个,黄连相关靶点246个,收集到350个T2DM相关靶点。相匹配后,得到42个人参、黄连药对治疗T2DM潜在靶点,其中,槲皮素(quercetin)、黄连素(berberine)、山奈酚(kaempferol)、花生四烯酸(arachidonate acid)、阿魏酸(ferulic acid)、豆甾醇(Stigmasterol)等6个成分能与3个及以上的关键靶点基因相连,可能是人参、黄连中治疗2型糖尿病的重要成分。结论人参、黄连药对靶点和药物代谢、胰岛素抵抗、炎症反应相关,并且参与了AMPK信号通路、NF-κB信号通路、TNF信号通路以及胰高血糖素信号通路,这些生物过程和信号通路可能是人参、黄连药对治疗T2DM的潜在机制。展开更多
OBJECTIVES:To observe the efficacy of Shenlian formula(SL formula,参连方),which consist of Huanglian(Rhizoma Coptidis)and Renshen(Radix Ginseng),in the treatment of type 2 diabetes mellitus(T2DM)and explore the effect...OBJECTIVES:To observe the efficacy of Shenlian formula(SL formula,参连方),which consist of Huanglian(Rhizoma Coptidis)and Renshen(Radix Ginseng),in the treatment of type 2 diabetes mellitus(T2DM)and explore the effects on gut microbiota and serum inflammatory cytokines.METHODS:In a double-blind,randomized,placebocontrolled parallel-group clinical trial,31 adults with T2DM were randomly allocated to receive the SL formula or placebo for 12 weeks.Body mass index(BMI),blood lipid indices,glycemic biomarkers including glycated hemoglobin(HbA1C),fasting plasma glucose(FPG),postprandial blood glucose(PBG),fasting insulin levels(FIL),fasting C-peptide(C-P),homoeostasis model assessment for insulin resistance(HOMA-IR)and inflammatory cytokines were assessed at baseline and 12 weeks.The contents of gut microbiota were determined by pyrosequencing of the V3-V4 regions of 16S rRNA genes.RESULTS:Sixteen cases were allocated in the treatment group and 15 in the placebo group.Compared with the placebo,SL formula resulted in a higher significant reduction in PBG[(-1.318±0.772)vs(-0.008±1.404)mmol/L,P=0.003],BMI[(-0.611±0.524)vs(0.957±2.212)kg/m2,P=0.01],FIL[(-1.627±6.268)vs(3.976±6.85)μIU/mL,P=0.02],HOMA-IR[(-0.530±1.461)vs(1.511±2.288),P=0.006],and C-reactive protein(CRP)[(-1.307±0.684)vs(0.828±0.557)mg/L,P=0.04].In terms of gut microbiota,compared with the placebo,the SL formula resulted in a significant decrease in species richness and evenness.CONCLUSIONS:The SL formula showed the efficacy to improve postprandial blood glucose,insulin resistance,BMI and CRP levels.In addition,it could reduce the total number,richness and evenness of species,meanwhile increase the abundance of probiotics to modulate the structure of gut microbiota in patients with T2DM.However,further studies are required for exploring the deeper mechanism of TCM on gut microbiota.展开更多
基金the National Key R&D Program of China:the Study on Syndrome Differentiation Standard of Yin Deficiency Syndrome in Type 2 Diabetes Mellitus(2018YFC1704402)the Project for Young Teachers of Beijing University of Chinese Medicine:Clinical Study on Intervention of Shenlian Formula based on Microbiota in Type 2 Diabetes Mellitus(No.2018-JYBZZ-JS062)。
文摘OBJECTIVES:To observe the efficacy of Shenlian formula(SL formula,参连方),which consist of Huanglian(Rhizoma Coptidis)and Renshen(Radix Ginseng),in the treatment of type 2 diabetes mellitus(T2DM)and explore the effects on gut microbiota and serum inflammatory cytokines.METHODS:In a double-blind,randomized,placebocontrolled parallel-group clinical trial,31 adults with T2DM were randomly allocated to receive the SL formula or placebo for 12 weeks.Body mass index(BMI),blood lipid indices,glycemic biomarkers including glycated hemoglobin(HbA1C),fasting plasma glucose(FPG),postprandial blood glucose(PBG),fasting insulin levels(FIL),fasting C-peptide(C-P),homoeostasis model assessment for insulin resistance(HOMA-IR)and inflammatory cytokines were assessed at baseline and 12 weeks.The contents of gut microbiota were determined by pyrosequencing of the V3-V4 regions of 16S rRNA genes.RESULTS:Sixteen cases were allocated in the treatment group and 15 in the placebo group.Compared with the placebo,SL formula resulted in a higher significant reduction in PBG[(-1.318±0.772)vs(-0.008±1.404)mmol/L,P=0.003],BMI[(-0.611±0.524)vs(0.957±2.212)kg/m2,P=0.01],FIL[(-1.627±6.268)vs(3.976±6.85)μIU/mL,P=0.02],HOMA-IR[(-0.530±1.461)vs(1.511±2.288),P=0.006],and C-reactive protein(CRP)[(-1.307±0.684)vs(0.828±0.557)mg/L,P=0.04].In terms of gut microbiota,compared with the placebo,the SL formula resulted in a significant decrease in species richness and evenness.CONCLUSIONS:The SL formula showed the efficacy to improve postprandial blood glucose,insulin resistance,BMI and CRP levels.In addition,it could reduce the total number,richness and evenness of species,meanwhile increase the abundance of probiotics to modulate the structure of gut microbiota in patients with T2DM.However,further studies are required for exploring the deeper mechanism of TCM on gut microbiota.
