College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Phytomedicine. 2019 Oct;63:152982. doi: 10.1016/j.phymed.2019.152982. Epub 2019 Jun 4.
SiNiSan (SNS) is a traditional Chinese medicine (TCM) prescription that has been widely used in the clinical treatment of irritable bowel syndrome (IBS). However, the underlying active substances and molecular mechanisms remain obscure.
A bioinformatics/topology based strategy was proposed for identification of the drug targets, therapeutic agents and molecular mechanisms of SiNiSan against irritable bowel syndrome.
In this work, a bioinformatics/network topology based strategy was employed by integrating ADME filtering, text mining, bioinformatics, network topology, Venn analysis and molecular docking to uncover systematically the multicomponent synergy mechanisms. In vivo experimental validation was executed in a Visceral Hypersensitivity (VHS) rat model.
76 protein targets and 109 active components of SNS were identified. Bioinformatics analysis revealed that 116 disease pathways associated with IBS therapy could be classified into the 19 statistically enriched functional sub-groups. The multi-functional co-synergism of SNS against IBS were predicted, including inflammatory reaction regulation, oxidative-stress depression regulation and hormone and immune regulation. The multi-component synergetic effects were also revealed on the herbal combination of SNS. The hub-bottleneck genes of the protein networks including PTGS2, CALM2, NOS2, SLC6A3 and MAOB, MAOA, CREB1 could become potential drug targets and Paeoniflorin, Naringin, Glycyrrhizic acid may be candidate agents. Experimental results showed that the potential mechanisms of SiNiSan treatment involved in the suppression of activation of Dopaminergic synapse and Amphetamine addiction signaling pathways, which are congruent with the prediction by the systematic approach.
The integrative investigation based on bioinformatics/network topology strategy may elaborate the multicomponent synergy mechanisms of SNS against IBS and provide the way out to develop new combination medicines for IBS.
思连康（SNS）是一种中药（TCM）处方，已广泛用于肠易激综合征（IBS）的临床治疗。然而，其潜在的活性物质和分子机制仍不清楚。
提出了一种基于生物信息学/拓扑学的策略，用于鉴定思连康治疗肠易激综合征的药物靶点、治疗剂和分子机制。
在这项工作中，采用了一种基于生物信息学/网络拓扑学的策略，通过整合 ADME 过滤、文本挖掘、生物信息学、网络拓扑学、Venn 分析和分子对接，系统地揭示了多成分协同作用机制。在内脏高敏性（VHS）大鼠模型中进行了体内实验验证。
鉴定出 76 个 SNS 蛋白靶点和 109 个活性成分。生物信息学分析表明，与 IBS 治疗相关的 116 种疾病途径可分为 19 个具有统计学意义的功能亚组。预测了 SNS 对 IBS 的多功能协同作用，包括炎症反应调节、氧化应激抑制调节和激素及免疫调节。还揭示了 SNS 草药组合的多成分协同作用。蛋白质网络的枢纽-瓶颈基因，包括 PTGS2、CALM2、NOS2、SLC6A3 和 MAOB、MAOA、CREB1，可能成为潜在的药物靶点，而芍药苷、柚皮苷、甘草酸可能是候选药物。实验结果表明，思连康治疗的潜在机制涉及抑制多巴胺能突触激活和安非他命成瘾信号通路，这与系统方法的预测结果一致。
基于生物信息学/网络拓扑学策略的综合研究可以阐明 SNS 治疗 IBS 的多成分协同作用机制，并为开发治疗 IBS 的新组合药物提供出路。
