摘要
目的 基于超高效液相色谱—高分辨质谱联用方法(ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry, UPLC-Q-TOF/MS)及网络药理学技术探究芪玉颗粒降血糖的作用机制。方法 利用UPLC-Q-TOF/MS技术对芪玉颗粒的入血成分进行研究,再以入血成分为药效成分进行网络药理学分析构建成分—靶点—疾病网络,预测芪玉颗粒治疗糖尿病可能的作用机制,并建立高糖高脂饲料联合小剂量链脲佐菌素诱导的糖尿病模型验证芪玉颗粒对糖尿病大鼠磷脂酰肌醇3-激酶(phosphoinositide 3-kinase, PI3K)-丝氨酸—苏氨酸激酶(threonine-protein kinase1, AKT)-磷酸化的糖原合成酶激酶-3β/糖原合成激酶3β(glycogen synthase kinase-3β,GSK-3β)通路的调节作用。结果 入血成分分析共鉴定出葛根素、黄芪甲苷、白杨素、大豆苷等17个原型成分和来源于咖啡酸、葛根素、阿魏酸、大豆苷等成分的69个代谢产物,结合网络药理学分析结果共得到肿瘤坏死因子(tumor necrosis factor, TNF)、丝氨酸—苏氨酸激酶1(threonine-protein kinase1, AKT1)等98个关键靶点及癌症的途径、胰岛素抵抗等144条通路。芪玉颗粒给药9周后,糖尿病大鼠血糖显著下降(P<0.001),PI3K、AKT、GSK-3β明显升高(P<0.01,P<0.05,P<0.001)。结论 通过血清药物化学结合网络药理学挖掘预测芪玉颗粒防治糖尿病的作用机制,为芪玉颗粒的降血糖作用机制研究及质控评价提供科学依据。动物实验初步证实了芪玉颗粒可通过调控PI3K-Akt-GSK-3β信号通路相关蛋白发挥预防治疗糖尿病的作用。
Objective Based on UPLC-Q-TOF/MS and network pharmacology technology,to explore the mechanism of Qiyu Granules in lowering blood sugar.Methods UPLC-Q-TOF/MS technology was used to study the blood entering components of Qiyu Granules,and then the network pharmacology analysis was conducted to construct the component target disease network with the blood entering components as the effective components,to predict the possible mechanism of Qiyu Granules in treating diabetes.And diabetes model was induced by high sugar and high fat diet combined with small dose streptozotocin(STZ)to verify the effect of Qiyu Granules on PI3K-Akt-GSK-3βin diabetes rats.Results Through blood component analysis,17 prototype components such as puerarin,astragaloside,albumen and daidzein were identified,and 69 metabolites derived from caffeic acid,puerarin,ferulic acid and daidzein were identified.tumor necrosis factor was obtained through network pharmacological analysis.(tumor necrosis factor,TNF),serine-threonine-protein kinase1(AKT1)and other 98 key targets and 144 pathways such as cancer pathways and insulin resistance were obtained ultimately.After 9 weeks of administration of Qiyu granules,the blood glucose of diabetic rats decreased significantly(P<0.001),phosphoinositide 3-kinase(PI3K),threonine-protein kinase(Threonine-kinase),and Phosphoinositide 3-kinase(PI3K).AKT,phosphorylated glycogen synthase kinase-3β/Glycogen synthase kinase-3β(GSK-3β)(P<0.01,P<0.05,P<0.001)significantly increased.Conclusion The mechanism of Qiyu Granules in preventing and treating diabetes can be predicted by combining serum pharmacochemistry with network pharmacology mining,which provides scientific basis for the study of Qiyu Granules’hypoglycemic mechanism and quality control evaluation.Animal experiments have preliminarily confirmed that Qiyu Granules can prevent and treat diabetes by regulating PI3K-Akt-GSK-3βsignal pathway related proteins.
作者
陶然
李一芃
叶丹妮
王梓旭
张丽梅
齐红
王林元
TAO Ran;LI Yipeng;YE Danni;WANG Zixu;ZHANG Limei;QI Hong;WANG Linyuan(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《环球中医药》
CAS
2024年第6期1065-1078,共14页
Global Traditional Chinese Medicine
基金
科技部重点研发计划中医药现代化重点专项(2018YFC1706801)。
