School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Phytomedicine. 2021 Jun;86:153527. doi: 10.1016/j.phymed.2021.153527. Epub 2021 Feb 24.
SiNiSan (SNS) is an ancient Chinese herbal prescription, and the current clinical treatment of irritable bowel syndrome (IBS) is effective. In the previous study of the research team, the multi-functional co-synergism of SNS against IBS was presented. Some potential drug targets and candidate ligands were predicted.
This study attempts to explore the crucial ingredient combinations from SNS formula and reveal their synergistic mechanism for IBS therapy.
In present study, a comprehensive strategy was performed to reveal IBS related pathways and biological modules, and explore synergistic effects of the ingredients, including ADME (absorption, distribution, metabolism, excretion) screening, Text mining, Venn analysis, Gene ontology (GO) analysis, Pathway cluster analysis, Molecular docking, Network construction and Experimental verification in visceral hypersensitivity (VHS) rats.
Three compressed IBS signal pathways were derived from ClueGO KEGG analysis of 63 IBS genes, including Neuroactive ligand-receptor interaction, Inflammatory mediator regulation of TRP (transient receptor potential) channels and Serotonergic synapse. A multi-module network, composed of four IBS therapeutic modules (psychological, inflammation, neuroendocrine and cross-talk modules), was revealed by Target-Pathway network. Nine kernel targets were considered closely associated with the IBS pathways, including ADRA2A, HTR2A, F2RL1, F2RL3, TRPV1, PKC, PKA, IL-1Β and NGF. In silico analysis revealed that three crucial ingredients (synephrine, paeoniflorin and naringin) were assumed to coordinate the network of those IBS therapeutic modules by acting on these kernel targets in the important pathways. In vivo experimental results showed that the crucial ingredient combinations synergistically affected the expressions of the kernel biological molecules, and improved the minimum capacity threshold of AWR in VHS rats.
The study proposes the important IBS associated pathways and the network regulation mechanisms of the crucial ingredients. It reveals the multi-target synergistic effect of the crucial ingredient combinations for the novel therapy on IBS.
思连康（SNS）是一种古老的中药配方，目前对肠易激综合征（IBS）的临床治疗有效。在研究小组的先前研究中，提出了 SNS 对 IBS 的多功能协同作用。预测了一些潜在的药物靶点和候选配体。
本研究试图探索 SNS 配方中的关键成分组合，并揭示其治疗 IBS 的协同机制。
本研究采用综合策略，揭示 IBS 相关途径和生物学模块，并探索成分的协同作用，包括 ADME（吸收、分布、代谢、排泄）筛选、文本挖掘、Venn 分析、GO 分析、途径聚类分析、分子对接、网络构建和内脏高敏性（VHS）大鼠的实验验证。
从 63 个 IBS 基因的 ClueGO KEGG 分析中得出三个压缩的 IBS 信号途径，包括神经活性配体-受体相互作用、TRP（瞬时受体电位）通道的炎症介质调节和 5-羟色胺能突触。通过靶-途径网络揭示了由四个 IBS 治疗模块（心理、炎症、神经内分泌和串扰模块）组成的多模块网络。九个核心靶点被认为与 IBS 途径密切相关，包括 ADRA2A、HTR2A、F2RL1、F2RL3、TRPV1、PKC、PKA、IL-1β和 NGF。计算机分析表明，三种关键成分（辛弗林、芍药苷和柚皮苷）通过作用于这些关键靶点，可能协同调节 IBS 治疗模块的网络。体内实验结果表明，关键成分组合协同影响核心生物分子的表达，并提高 VHS 大鼠 AWR 的最小容量阈值。
该研究提出了重要的 IBS 相关途径和关键成分的网络调节机制。它揭示了关键成分组合对 IBS 新型治疗的多靶点协同作用。
