Exploring the Potential Molecular Mechanism of the Shugan Jieyu Capsule in the Treatment of Depression through Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation


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Abstract

Background:Shugan Jieyu Capsule (SJC) is a pure Chinese medicine compound prepared with Hypericum perforatum and Acanthopanacis senticosi. SJC has been approved for the clinical treatment of depression, but the mechanism of action is still unclear.

Objective: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.

Methods:TCMSP, BATMAN-TCM, and HERB databases were used, and related literature was reviewed to screen the effective active ingredients of Hypericum perforatum and Acanthopanacis Senticosi. 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.

Results: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.

Conclusion: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.

About the authors

Zhiyao Liu

Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Hailiang Huang

Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Ying Yu

Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Yuqi Jia

Innovative Institute of Chinese Medicine and Pharmacy,, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Lingling Li

Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Xin Shi

Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

Fangqi Wang

Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine

Email: info@benthamscience.net

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