College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
J Ethnopharmacol. 2019 Apr 6;233:158-168. doi: 10.1016/j.jep.2018.12.033. Epub 2018 Dec 24.
Banxia Xiexin Decoction (BXD) is a representative prescription to regulate spleen and stomach in "Treatise on Febrile Diseases", which has been proven effective for the clinical treatment of irritable bowel syndrome (IBS) in the past decades. However, the active principles and molecular mechanisms involved in BXD against IBS are vague yet.
To unfold multicomponent synergy mechanism of BXD on irritable bowel syndrome, this work explored active principles, drug targets and crucial pathways using a systems pharmacology strategy.
In this study, a systems pharmacology based strategy was applied by the procedures integrating compound database construction, ADME evaluation, target identification, functional annotation, pathway enrichment analysis, network analysis, and molecular docking verification. The 158 compounds from BXD were selected for the screening. The Compound-Target network (C-T) and the Target-Pathway network (T-P) were constructed. The bioinformatics and network topology were employed to systematically reveal multicomponent-target interactions of BXD. The affinity between important ingredients and the kernel targets was validated using molecular mechanics simulation.
The 35 potential important ingredients and the 16 associated kernel targets were identified. 27 crucial pathways, in which the kernel targets participated, could regulate the biological processes, such as synthesis of inflammatory mediators, smooth muscle relaxation and synaptic plasticity, closely related to pathological mechanism of IBS. The cross-talk interactions were revealed between TNF signaling pathway, Dopaminergic synapse and cGMP-PKG signaling pathway, which would exert the synergistic influences on the occurrence and treatment of the IBS. PTGS2, CALM, NOS2, SCN5A, and PRSS1 might become novel drug targets for IBS.
The study demonstrated that the synergy molecular mechanisms of BXD mainly involved three therapeutic modules including inhibiting inflammatory reaction, maintaining intestinal function and improving psychological regulation via the multicomponent-target interaction networks. It may also provide the promising drug targets and therapeutic agents for the development of new medicines.
半夏泻心汤（BXD）是《伤寒论》中调节脾胃的代表性方剂，几十年来已被证明对治疗肠易激综合征（IBS）有效。然而，BXD 治疗 IBS 的活性成分和分子机制尚不清楚。
本研究采用系统药理学策略，探索 BXD 治疗肠易激综合征的多成分协同作用机制，研究活性成分、药物靶点和关键途径。
本研究采用系统药理学策略，通过整合化合物数据库构建、ADME 评价、靶点鉴定、功能注释、通路富集分析、网络分析和分子对接验证等程序进行。筛选出 BXD 的 158 种化合物。构建了化合物-靶点网络（C-T）和靶点-通路网络（T-P）。采用生物信息学和网络拓扑学方法系统揭示 BXD 的多成分-靶点相互作用。利用分子力学模拟验证重要成分与核心靶点的亲和力。
确定了 35 种潜在的重要成分和 16 个相关的核心靶点。27 个关键通路，其中核心靶点参与，可调节与 IBS 病理机制密切相关的生物过程，如炎症介质合成、平滑肌松弛和突触可塑性。TNF 信号通路、多巴胺能突触和 cGMP-PKG 信号通路之间存在交叉对话相互作用，对 IBS 的发生和治疗会产生协同影响。PTGS2、CALM、NOS2、SCN5A 和 PRSS1 可能成为 IBS 的新药物靶点。
研究表明，BXD 的协同作用机制主要涉及三个治疗模块，包括抑制炎症反应、维持肠道功能和改善心理调节，通过多成分-靶点相互作用网络发挥作用。它还可能为新药的开发提供有前途的药物靶点和治疗剂。
