基于生物网络功能模块整合组方规律分析四黄止痢颗粒治疗仔猪腹泻的作用机制

doi:10.11843/j.issn.0366-6964.2023.07.034

畜牧兽医学报 ›› 2023, Vol. 54 ›› Issue (7): 3031-3043.doi: 10.11843/j.issn.0366-6964.2023.07.034

基于生物网络功能模块整合组方规律分析四黄止痢颗粒治疗仔猪腹泻的作用机制

周炜炜¹, 王雪峰², 张梦洁¹, 杨娟¹, 孙悦龙¹, 张祖烽², 张宇欣², 豆佳红³, 王梓颖³, 戴小枫^1*, 李秀梅^1*

1. 中国农业科学院饲料研究所农业农村部饲料生物技术重点实验室, 北京 100081;
2. 哈尔滨商业大学药学院, 哈尔滨 150076;
3. 天津科技大学生物工程学院, 天津 300457

收稿日期:2022-08-18 出版日期:2023-07-23 发布日期:2023-07-21
通讯作者: 戴小枫,主要从事药食同源中草药研究,E-mail:daixiaofeng@caas.cn;李秀梅,主要从事天然植物提取物及其功能组分实现动物绿色生产的关键核心技术研究,E-mail:lixiumei@caas.cn
作者简介:周炜炜(1992-),女,湖北宜昌人,助理研究员,博士,主要从事饲用中草药研究,E-mail:zhouweiwei@caas.cn
基金资助:
农业农村部饲料生物技术重点实验室开放课题（KLFB-FRI-202104）；中国农科院创新工程联合攻关重大科研任务（CAAS-ZDRW202111）

Analysing the Mechanism of Sihuang Zhili Granule in the Treatment of Piglet Diarrhea Based on Biological Network Function Modules and Compatibility Rules

ZHOU Weiwei¹, WANG Xuefeng², ZHANG Mengjie¹, YANG Juan¹, SUN Yuelong¹, ZHANG Zufeng², ZHANG Yuxin², DOU Jiahong³, WANG Ziying³, DAI Xiaofeng^1*, LI Xiumei^1*

1. Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research of Chinese Academy of Agricultural Sciences, Beijing 100081, China;
2. College of Pharmacy, Harbin University of Commerce, Harbin 150076, China;
3. College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China

Received:2022-08-18 Online:2023-07-23 Published:2023-07-21

摘要/Abstract

摘要： 从功能模块水平研究中药复方四黄止痢颗粒治疗仔猪腹泻的分子作用机制，并阐释其配伍规律。使用TCMSP、TCMID、HERB数据库筛选方中黄连、黄柏、大黄、黄芩、板蓝根、甘草6味中药的有效成分，收集相关药物靶点；使用GeneCards、NCBI、OMIM数据库获取仔猪腹泻的疾病靶点；比较分析药物靶点和疾病靶点的交集并用韦恩图表示，将其上传至STRING数据库进行蛋白相互作用分析；采用Cytoscape软件绘制靶点蛋白相互作用网络图（protein-protein interaction network，PPI）；应用MCODE插件对PPI网络进行功能模块识别；运用David数据库对功能模块进行KEGG通路富集分析。结果表明：1）网络分析筛选活性成分180个，主要包括生物碱、黄酮、蒽醌、苷类成分；药物靶点蛋白88个，猪腹泻相关靶点470个，二者的交集靶点35个。2）蛋白互作网络分析表明，由17个靶点蛋白组成的模块1是中药复方四黄止痢颗粒的功能模块。3） KEGG富集分析表明，模块1主要涉及的通路包括TNF、IL-17以及NF-κB等17个信号通路。4）归经分析表明，四黄止痢颗粒主要作用于脾、胃等11个脏腑经络。综上所述，生物碱、黄酮、蒽醌、苷类成分是四黄止痢颗粒的物质基础，主要通过作用于功能模块1调控TNF、IL-17、NF-κB等信号通路，调节脾、胃等脏腑经络，从蛋白靶点、信号通路以及经络等多个水平上发挥治疗仔猪腹泻的作用。

关键词: 生物网络, 功能模块, 四黄止痢颗粒, 仔猪腹泻, 作用机制

Abstract: The aim of this study was to explore the molecular mechanism of Sihuang Zhili Granule in the treatment of piglet diarrhea based on the functional module, and to explain its compatibility law. TCMSP, TCMID and HERB databases were used to screen the active ingredients of Coptidis Rhizoma, Phellodendri Chinensis Cortex, Rhei Radix et Rhizoma, Scutellariae Radix, Isatidis Radix, Glycyrrhizae Radix et Rhizoma, and collect the related targets. Disease targets of piglet diarrhea were selected from GeneCards、NCBI、OMIM database. Then, the intersection of drug targets and the disease targets were collected by Venny platform, and uploaded to the STRING database for protein interaction analysis. Protein-protein interaction (PPI) network was constructed by Cytoscape software, and its functional module was identified with MCODE plug-in. KEGG pathway enrichment analysis was performed with David database. The results were showed as follows:1) Network analysis showed that a total of 180 active ingredients were obtained, mainly included alkaloids, flavonoids, anthraquinones and glycosides; A total of 88 drug targets and 470 disease targets were screened, and there were 35 intersection targets. 2) The PPI network analysis showed that module 1 composed of 17 target proteins was the functional module of Sihuang Zhili granules. 3) The KEGG enrichment analysis determined that the pathways mainly involved in module 1 include 17 signaling pathways such as TNF, IL-17 and NF-κB. 4) The analysis of meridians showed that Sihuang Zhili granule could act on 11 collateral channels of internal organs of animal body, and mainly on spleen and stomach meridians. In conclusion, alkaloids, flavonoids, anthraquinone and glycosides are the material basis of Sihuang Zhili granules. They mainly regulate the signaling pathways such as TNF, IL-17 and NF-κB by acting on the key targets included in functional module 1, regulate multiple meridians of the body such as spleen and stomach, and play the role of treating piglet diarrhea from multiple levels such as protein targets, signaling pathways and meridians.

Key words: biological network, functional module, Sihuang Zhili granule, piglet diarrhea, mechanism

中图分类号:

S853.9

周炜炜, 王雪峰, 张梦洁, 杨娟, 孙悦龙, 张祖烽, 张宇欣, 豆佳红, 王梓颖, 戴小枫, 李秀梅. 基于生物网络功能模块整合组方规律分析四黄止痢颗粒治疗仔猪腹泻的作用机制[J]. 畜牧兽医学报, 2023, 54(7): 3031-3043.

ZHOU Weiwei, WANG Xuefeng, ZHANG Mengjie, YANG Juan, SUN Yuelong, ZHANG Zufeng, ZHANG Yuxin, DOU Jiahong, WANG Ziying, DAI Xiaofeng, LI Xiumei. Analysing the Mechanism of Sihuang Zhili Granule in the Treatment of Piglet Diarrhea Based on Biological Network Function Modules and Compatibility Rules[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 3031-3043.

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基于生物网络功能模块整合组方规律分析四黄止痢颗粒治疗仔猪腹泻的作用机制

Analysing the Mechanism of Sihuang Zhili Granule in the Treatment of Piglet Diarrhea Based on Biological Network Function Modules and Compatibility Rules

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