药学学报, 2020, 55(12): 2934-2941
引用本文:
董雅倩, 张佳幸, 龚琳娜, 石碧锐, 周凤华, 肖炜, 刘孟华. 白花蛇舌草环烯醚萜的鉴定及基于网络药理学的抗肾纤维化作用的机制研究[J]. 药学学报, 2020, 55(12): 2934-2941.
DONG Ya-qian, ZHANG Jia-xing, GONG Lin-na, SHI Bi-rui, ZHOU Feng-hua, XIAO Wei, LIU Meng-hua. Identification of the iridoids of Hedyotis diffusa Willd and its mechanism on renal fibrosis based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2934-2941.

白花蛇舌草环烯醚萜的鉴定及基于网络药理学的抗肾纤维化作用的机制研究
董雅倩1, 张佳幸2, 龚琳娜1, 石碧锐1, 周凤华2, 肖炜2, 刘孟华1
1. 南方医科大学药学院, 广东 广州 510515;
2. 南方医科大学中医药学院, 广东 广州 510515
摘要:
白花蛇舌草环烯醚萜的鉴定及基于网络药理学对其抗肾纤维化作用的机制研究。运用液相色谱-四极杆-飞行时间质谱(liquid chromatograpy-quadrupole/time of flight mass spectrometry,LC-Q/TOF-MS)技术对白花蛇舌草环烯醚萜类成分进行分析鉴定;通过DisGeNET和MalaCards数据库检索与肾脏纤维化相关靶点;利用SYBYL-X7.3软件进行分子对接,筛选出化合物作用的潜在靶点;通过构建化合物-靶点网络和蛋白互作(protein-protein interaction,PPI)网络,进行基因本体(gene ontology,GO)功能富集分析和KEGG通路富集分析,探究环烯醚萜类成分治疗肾纤维化的作用机制。结果发现化合物-靶点网络包含10个化合物和111个相关靶点,关键靶点涉及二甲基精氨酸二甲胺水解酶1(dimethylarginine dimethylaminohydrolase 1,DDAH1)、乙酰肝素酶(heparanase,HPSE)、人源鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)及膜突蛋白(moesin,MSN)等。GO功能富集分析得到GO条目211个。KEGG通路富集分析筛选出20条信号通路,涉及Toll样受体信号通路(Toll-like receptor signaling pathway)、转化生长因子(transforming growth factor-beta,TGF-β)信号通路、肾细胞癌(renal cell carcinoma)信号通路和Janus激酶/信号转导与转录激活子(the Janus kinase/signal transducer and activator of tran-ions,Jak-STAT)信号通路等。本文初步探讨了白花蛇舌草环烯醚萜化合物治疗肾纤维化的分子机制,为后续实验研究及临床应用提供先导信息。
关键词:    白花蛇舌草      环烯醚萜      网络药理学      肾纤维化      作用机制     
Identification of the iridoids of Hedyotis diffusa Willd and its mechanism on renal fibrosis based on network pharmacology
DONG Ya-qian1, ZHANG Jia-xing2, GONG Lin-na1, SHI Bi-rui1, ZHOU Feng-hua2, XIAO Wei2, LIU Meng-hua1
1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China;
2. College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
Abstract:
To identify the composition of iridoids from Hedyotis diffusa Willd and explore the mechanism on its anti-renal fibrosis effect based on network pharmacology, LC-Q/TOF-MS (liquid chromatograpy-quadrupole/time of flight mass spectrometry) was used to analyze the iridoid ingredients and the related targets of renal fibrosis were obtained by DisGeNET database and MalaCards database. The potential targets were screened by SYBYL-X7.3 software. We then imported the identified ingredients and potential target genes into Cytoscape3.7.1 to construct the compound-target network and the protein-protein interaction (PPI) network. Finally, the gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis of the selected core genes were made to explore the mechanism of iridoids against renal fibrosis. There were 10 active iridoid compounds and 111 corresponding targets including dimethylarginine dimethylaminohydrolase 1 (DDAH1), heparanase (HPSE), human kirsten rat sarcoma viral oncogene (KRAS), moesin (MSN), etc. in compound-target network. The GO functional enrichment analysis obtained 211 GO entries. Twenty related signal pathways including Toll-like receptor signaling pathway, transforming growth factor-beta (TGF-β) signaling pathway, renal cell carcinoma signaling pathway, and the Janus kinase/signal transducer and activator of tran-ions (Jak-STAT) signaling pathway were selected by KEGG enrichment analysis. We preliminarily investigated the mechanism of the iridoid compounds on renal fibrosis to provide guide information for the subsequent experimental research and clinical application.
Key words:    Hedyotis diffusa Willd    iridoid    network pharmacology    renal fibrosis    mechanism   
收稿日期: 2020-05-11
DOI: 10.16438/j.0513-4870.2020-0727
基金项目: 国家自然科学基金资助项目(81774213);广东省自然科学基金项目(2017A030313750);大学生创新创业训练计划项目(201912121034).
通讯作者: 刘孟华,Tel/Fax:86-20-61648597,E-mail:liumenghua@smu.edu.cn
Email: liumenghua@smu.edu.cn
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