title: A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components.
abstract: Chinese medicine is known to treat complex diseases with multiple components and multiple targets. However, the main effective components and their related key targets and functions remain to be identified. Herein, a network analysis method was developed to identify the main effective components and key targets of a Chinese medicine, Lianhua-Qingwen Formula (LQF). The LQF is commonly used for the prevention and treatment of viral influenza in China. It is composed of 11 herbs, gypsum and menthol with 61 compounds being identified in our previous work. In this paper, these 61 candidate compounds were used to find their related targets and construct the predicted-target (PT) network. An influenza-related protein-protein interaction (PPI) network was constructed and integrated with the PT network. Then the compound-effective target (CET) network and compound-ineffective target network (CIT) were extracted, respectively. A novel approach was developed to identify effective components by comparing CET and CIT networks. As a result, 15 main effective components were identified along with 61 corresponding targets. 7 of these main effective components were further experimentally validated to have antivirus efficacy in vitro. The main effective component-target (MECT) network was further constructed with main effective components and their key targets. Gene Ontology (GO) analysis of the MECT network predicted key functions such as NO production being modulated by the LQF. Interestingly, five effective components were experimentally tested and exhibited inhibitory effects on NO production in the LPS induced RAW 264.7 cell. In summary, we have developed a novel approach to identify the main effective components in a Chinese medicine LQF and experimentally validated some of the predictions.
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Yue-Fei
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Jia
authors.affiliation: Institute of TCM and Natural Medicine, Jinan University, Guangzhou 510632, China. twangguocai@jnu.edu.cn.
authors.forename: Guo-Cai
authors.initials: GC
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lizheng1@gmail.com +86-571-88208427.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Gao
mesh_terms: D000465:Algorithms; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D060066:Protein Interaction Maps; D000067996:RAW 264.7 Cells
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; C000588632:lianhuaqingwen; D009569:Nitric Oxide