药学学报, 2019, 54(11): 2019-2030
引用本文:
秦惠玉, 张彤, 王忠英, 陈文, 韩博. 基于系统药理学的毛菊苣醇提物治疗2型糖尿病伴随非酒精性脂肪肝作用及机制研究[J]. 药学学报, 2019, 54(11): 2019-2030.
QIN Hui-yu, ZHANG Tong, WANG Zhong-ying, CHEN Wen, HAN Bo. The action and mechanism of ethanol extract of Cichorium glandulosum on type 2 diabetes mellitus accompanied with nonalcoholic fatty liver disease based on systems pharmacology[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 2019-2030.

基于系统药理学的毛菊苣醇提物治疗2型糖尿病伴随非酒精性脂肪肝作用及机制研究
秦惠玉1, 张彤1,2, 王忠英1, 陈文1, 韩博1
1. 石河子大学药学院, 新疆 石河子 832002;
2. 北京科兴生物制品有限公司, 北京 100085
摘要:
毛菊苣在维吾尔族民间被用于治疗非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)和2型糖尿病(type 2 diabetes mellitus),但其治疗2型糖尿病伴随非酒精性脂肪肝(T2DM-NAFLD)的作用机制尚不明确。本研究通过动物实验对毛菊苣提取物治疗T2DM-NAFLD的作用进行研究(本动物实验经石河子大学医学院第一附属医院实验动物伦理审查委员会批准);运用系统药理学筛选并预测毛菊苣治疗T2DM-NAFLD的靶点、通路和疾病,构建和分析化合物-靶点-通路和化合物-靶点-疾病关系网络。动物实验表明,毛菊苣提取物可改善T2DM-NAFLD大鼠的血糖血脂水平,增加糖耐量并减轻肝损伤。通过系统药理学筛选得到毛菊苣中29个可能的活性成分、198个靶点,其中涉及T2DM的靶点106个,涉及NAFLD的靶点88个,T2DM和NAFLD共有的靶点56个,这些靶点主要参与代谢通路、钙信号通路、PI3K/Akt信号通路、cAMP通路、MAPK通路等,与胰岛素抵抗和炎症有关。毛菊苣可能是治疗T2DM-NAFLD的候选草药,本工作为研究多靶点植物药治疗多种疾病提供了系统药理学角度的参考。
关键词:    毛菊苣      2型糖尿病伴随非酒精性脂肪肝      系统药理学      活性成分     
The action and mechanism of ethanol extract of Cichorium glandulosum on type 2 diabetes mellitus accompanied with nonalcoholic fatty liver disease based on systems pharmacology
QIN Hui-yu1, ZHANG Tong1,2, WANG Zhong-ying1, CHEN Wen1, HAN Bo1
1. School of Pharmacy, Shihezi University, Shihezi 832002, China;
2. Sinovac Biotech CO., Ltd., Beijing 100085, China
Abstract:
Cichorium glandulosum has been used to treat non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) in Uyghur folk medicine. The mechanism of Cichorium glandulosum (CG) on type 2 diabetes mellitus accompanied with non-alcoholic fatty liver disease (T2DM-NAFLD) remains unclear. The effect of CG extraction on T2DM-NAFLD was determined in animal experiments here (all the experiments here were approved by the Animal Care Committee of the First Affiliated Hospital of the Medical College, Shihezi University). The mechanism of CG for treatment of T2DM-NAFLD was predicted and verified based on systems pharmacology. Based on the active compounds of CG on T2DM-NAFLD, T2DM and NAFLD-related targets, pathways and diseases were screened and predicted. Active compounds-targets, compounds-targets-pathways and compounds-targets-diseases were constructed and analyzed. The results of animal experiments showed that CG extraction can reduce the levels of blood glucose and blood lipid in T2DM-NAFLD rats. In addition, it can improve the glucose tolerance and relieve liver injury. Total 29 active compounds and 198 targets were screened by systems pharmacology, of which 106 targets were involved in T2DM, 88 were involved in NAFLD, and 56 targets were common between T2DM and NAFLD, mainly related to insulin resistance and inflammation. These 198 targets include those in metabolic pathways, calcium pathway, PI3K/Akt pathway, cAMP pathway, and MAPK pathway. Our study confirmed that CG can be potential phytomedicine for treatment of T2DM-NAFLD. This work provides a reference for studying the treatment of multiple diseases using multiple-targets phytomedicine in systems pharmacology.
Key words:    Cichorium glandulosum    type 2 diabetes mellitus accompanied with non-alcoholic fatty liver disease    systems pharmacology    active compound   
收稿日期: 2019-02-13
DOI: 10.16438/j.0513-4870.2019-0114
基金项目: 国家自然科学基金资助项目(81760756);石河子大学杰出青年科技人才培育计划(2015ZRKXJQ08).
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