Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
High Level Key Disciplines of Traditional Chinese Medicine Basic Theory of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Curr Comput Aided Drug Des. 2024;20(5):501-517. doi: 10.2174/1573409919666230619105254.
Shugan Jieyu Capsule (SJC) is a pure Chinese medicine compound prepared with and . SJC has been approved for the clinical treatment of depression, but the mechanism of action is still unclear.
Network pharmacology, molecular docking, and molecular dynamics simulation (MDS) were applied in the present study to explore the potential mechanism of SJC in the treatment of depression.
TCMSP, BATMAN-TCM, and HERB databases were used, and related literature was reviewed to screen the effective active ingredients of and . TCMSP, BATMAN-TCM, HERB, and STITCH databases were used to predict the potential targets of effective active ingredients. GeneCards database, DisGeNET database, and GEO data set were used to obtain depression targets and clarify the intersection targets of SJC and depression. STRING database and Cytoscape software were used to build a protein-protein interaction (PPI) network of intersection targets and screen the core targets. The enrichment analysis on the intersection targets was conducted. Then the receiver operator characteristic (ROC) curve was constructed to verify the core targets. The pharmacokinetic characteristics of core active ingredients were predicted by SwissADME and pkCSM. Molecular docking was performed to verify the docking activity of the core active ingredients and core targets, and molecular dynamics simulations were performed to evaluate the accuracy of the docking complex.
We obtained 15 active ingredients and 308 potential drug targets with quercetin, kaempferol, luteolin, and hyperforin as the core active ingredients. We obtained 3598 targets of depression and 193 intersection targets of SJC and depression. A total of 9 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2) were screened with Cytoscape 3.8.2 software. A total of 442 GO entries and 165 KEGG pathways (p <0.01) were obtained from the enrichment analysis of the intersection targets, mainly enriched in IL-17, TNF, and MAPK signaling pathways. The pharmacokinetic characteristics of the 4 core active ingredients indicated that they could play a role in SJC antidepressants with fewer side effects. Molecular docking showed that the 4 core active components could effectively bind to the 8 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2), which were related to depression by the ROC curve. MDS showed that the docking complex was stable.
SJC may treat depression by using active ingredients such as quercetin, kaempferol, luteolin, and hyperforin to regulate targets such as PTGS2 and CASP3 and signaling pathways such as IL-17, TNF, and MAPK, and participate in immune inflammation, oxidative stress, apoptosis, neurogenesis, etc.
舒肝解郁胶囊（SJC）是一种由 和 制成的纯中药复方制剂。SJC 已被批准用于治疗抑郁症，但作用机制仍不清楚。
本研究采用网络药理学、分子对接和分子动力学模拟（MDS）方法，探讨 SJC 治疗抑郁症的潜在作用机制。
利用 TCMSP、BATMAN-TCM 和 HERB 数据库，结合相关文献，筛选 和 的有效活性成分。利用 TCMSP、BATMAN-TCM、HERB 和 STITCH 数据库预测有效活性成分的潜在靶点。利用 GeneCards 数据库、DisGeNET 数据库和 GEO 数据集获取抑郁症靶点，并明确 SJC 与抑郁症的交集靶点。利用 STRING 数据库和 Cytoscape 软件构建交集靶点的蛋白质-蛋白质相互作用（PPI）网络，并筛选核心靶点。对交集靶点进行富集分析，然后构建受试者工作特征（ROC）曲线以验证核心靶点。利用 SwissADME 和 pkCSM 预测核心活性成分的药代动力学特征。进行分子对接，验证核心活性成分和核心靶点的对接活性，并用分子动力学模拟评估对接复合物的准确性。
得到了以槲皮素、山奈酚、木犀草素和贯叶连翘素为核心活性成分的 15 种活性成分和 308 个潜在药物靶点。得到了 3598 个抑郁症靶点和 SJC 与抑郁症的 193 个交集靶点。利用 Cytoscape 3.8.2 软件筛选出 9 个核心靶点（AKT1、TNF、IL6、IL1B、VEGFA、JUN、CASP3、MAPK3、PTGS2）。交集靶点的富集分析得到了 442 个 GO 条目和 165 个 KEGG 通路（p<0.01），主要富集在 IL-17、TNF 和 MAPK 信号通路。4 种核心活性成分的药代动力学特征表明，它们可能通过较少的副作用发挥 SJC 抗抑郁作用。分子对接表明，4 种核心活性成分可以通过 ROC 曲线有效结合到与抑郁症相关的 8 个核心靶点（AKT1、TNF、IL6、IL1B、VEGFA、JUN、CASP3、MAPK3、PTGS2）。MDS 表明对接复合物稳定。
SJC 可能通过调节 PTGS2 和 CASP3 等靶点和 IL-17、TNF、MAPK 等信号通路，参与免疫炎症、氧化应激、细胞凋亡、神经发生等过程，发挥抗抑郁作用，其有效活性成分可能为槲皮素、山奈酚、木犀草素和贯叶连翘素等。
