药学学报, 2021, 56(2): 528-537
引用本文:
高耀, 穆俊芳, 令狐婷, 周玉枝, 高晓霞, 田俊生, 秦雪梅. 逍遥散治疗抑郁症代谢网络的模块划分与生物学机制研究[J]. 药学学报, 2021, 56(2): 528-537.
GAO Yao, MU Jun-fang, LING-HU Ting, ZHOU Yu-zhi, GAO Xiao-xia, TIAN Jun-sheng, QIN Xue-mei. Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 528-537.

逍遥散治疗抑郁症代谢网络的模块划分与生物学机制研究
高耀1,2, 穆俊芳3, 令狐婷1,2, 周玉枝1,2, 高晓霞1,2, 田俊生1,2, 秦雪梅1,2
1. 山西大学中医药现代研究中心, 山西 太原 030006;
2. 地产中药功效物质研究与利用山西省重点实验室, 山西 太原 030006;
3. 山西大学计算机与信息技术学院, 山西 太原 030006
摘要:
逍遥散的抗抑郁作用已经明确,应用代谢网络的功能模块划分方法,从功能模块角度探究逍遥散治疗抑郁症的生物学机制具有重要意义和价值。通过数据库收集逍遥散调节差异代谢物、差异代谢物相关的酶以及与抑郁症相关的蛋白,对逍遥散调节差异代谢物进行通路富集分析和交互分析,利用STRING工具构建差异代谢物相关的酶与抑郁症的蛋白网络,应用CNM分解算法提取网络蛋白功能模块并进行功能模块富集分析。结果发现,逍遥散调节差异代谢物97个、差异代谢物相关酶234个、抑郁症相关蛋白258个。通路交互分析划分为2个子网络,其中一个为神经系统和细胞信号转导相关通路,另一个为内分泌系统和代谢途径相关通路。对蛋白网络以及使用CNM算法从中提取的9个蛋白功能模块进行KEGG通路富集分析,结果发现模块1和模块3属于可用较少的蛋白富集到较多的通路,这些通路对应的功能包括内分泌系统、氨基酸代谢、神经系统和信号转导等。本研究采用通路交互分析和代谢网络模块划分策略阐释逍遥散治疗抑郁症的生物学机制,为从代谢调控角度深入研究中药复方药理作用机制提供思路参考和方法借鉴。
关键词:    逍遥散      抑郁症      通路交互分析      功能模块      核心蛋白     
Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression
GAO Yao1,2, MU Jun-fang3, LING-HU Ting1,2, ZHOU Yu-zhi1,2, GAO Xiao-xia1,2, TIAN Jun-sheng1,2, QIN Xue-mei1,2
1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China;
2. Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Taiyuan 030006, China;
3. School of Computer and Information Technology, Shanxi University, Taiyuan 030006, China
Abstract:
The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.
Key words:    Xiaoyaosan    depression    pathway crosstalk analysis    functional module    core protein   
收稿日期: 2020-06-30
DOI: 10.16438/j.0513-4870.2020-1079
基金项目: 国家“重大新药创制”科技重大专项(2017ZX09301047);国家自然科学基金资助项目(82074147);山西省科技重点研发计划(201903D321210);山西省重点实验室项目(201605D111004);山西省科技创新重点团队项目(201605D131045-18);山西省应用基础研究项目(201801D121291);山西省“1331工程”协同创新中心建设计划经费资助.
通讯作者: 田俊生,Tel:86-351-7018379,E-mail:qinxm@sxu.edu.cn;秦雪梅,E-mail:jstian@sxu.edu.cn
Email: qinxm@sxu.edu.cn;jstian@sxu.edu.cn
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