Mechanisms of Compound Kushen Injection for Treatment of Bladder Cancer Based on Bioinformatics and Network Pharmacology With Experimental Validation

2020 ◽  
Author(s):  
Lihui Zhang ◽  
Wanying Zhang ◽  
Jiaming Xiong ◽  
Xiumei Duan ◽  
Lina Hai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Target Genes ◽  
Medicinal Preparation ◽  
Malignant Neoplasm ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Bladder Cancer Cell Line ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Gene And Protein Expression

Abstract Background: Bladder cancer is the most common malignant neoplasm of the urinary system. CompoundKushen injection (CKI) is a Chinese medicinal preparation that has been used clinically to treat varioustypes of cancers for more than 20 years. However, the pharmacological effect of CKI on bladder cancerrequires further clarification.Methods: Network pharmacology combined with bioinformatics was used to elucidate the therapeuticmechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI is effective againstbladder cancer was further verified in vitro using the human bladder cancer cell line T24.Results: Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data mining revealed 5500 differentially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerts anti-bladder cancer effects byregulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated thatCKI has a therapeutic effect on bladder cancer by synergistically regulating certain biological processes,including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes andGenomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Aktsignaling pathway. Consistently, cell experiments indicated that CKI could inhibit proliferation andmigration of T24 bladder cancer cells, and induce their apoptosis. Moreover, RT-qPCR and western blotresults indicated that CKI may treat bladder cancer by downregulating gene and protein expression levels,respectively of MMP-9, JUN, EGFR, and ERK1.Conclusions: CKI can inhibit proliferation and migration, and induce apoptosis of T24 bladder cancer cellsthrough multiple biological pathways and targets. CKI also has significant effects on regulation of key genesand proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen currentunderstanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Uncovering Active Ingredients and Mechanisms of Spica Prunellae in the Treatment of Colon Adenocarcinoma: A Study Based on Network Pharmacology and Bioinformatics

2020 ◽  
Vol 23 ◽  
Author(s):  
Yan Lei ◽  
Hao Yuan ◽  
Liyue Gai ◽  
Xuelian Wu ◽  
Zhixiao Luo
Keyword(s):  
Target Genes ◽  
Experimental Studies ◽  
Colon Adenocarcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Ppi Network ◽  
Active Ingredients ◽  
Hub Genes

Background: As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanism of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics. Methods: A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study. Results: We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified.Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathway. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from whichTP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared differential expression level and assessed prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3. Conclusion: In this study, active ingredients and mechanism of SPin the treatment of COAD were systematically dis-cussed, which providedthe foundation for further experimental studies and mightact to promote its appropriate clinical application.

scholarly journals Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases

2021 ◽  
Author(s):  
Jie-wen Zhao ◽  
Hai-dong Liu ◽  
Ming-yin Man ◽  
Lv-ya Wang ◽  
Ning Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cardiovascular Diseases ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Therapeutic Effects ◽  
Active Components

Abstract Background Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD). Results From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients. Conclusion These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.

scholarly journals Network Pharmacology-Based Approach to Investigate the Mechanisms ofHedyotis diffusaWilld. in the Treatment of Gastric Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Xinkui Liu ◽  
Jiarui Wu ◽  
Dan Zhang ◽  
Kaihuan Wang ◽  
Xiaojiao Duan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Enrichment Analysis ◽  
Cyclin B1 ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Ras Signaling ◽  
Therapeutic Effects

Background.Hedyotis diffusaWilld. (HDW) is one of the renowned herbs often used in the treatment of gastric cancer (GC). However, its curative mechanism has not been fully elucidated.Objective. To systematically investigate the mechanisms of HDW in GC.Methods. A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study.Results. A total of 353 targets of the 32 bioactive compounds in HDW were obtained. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2,P27Kip1, cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway.Conclusions. This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis.

Study on the Anti-Tumor Mechanism and Target of Triptolide based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 16 ◽  
Author(s):  
Tao Zou ◽  
Yuanqiong Huang ◽  
Yifan Hu ◽  
Mingyu Wu ◽  
Yueshui Zhao ◽  
...  
Keyword(s):  
Target Genes ◽  
Inflammatory Responses ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Specific Target ◽  
Pharmacological Mechanism ◽  
The Core ◽  
Core Genes

Background: According to the special physiological and pharmacological activities of natural compounds, many drugs with special therapeutic effects have been developed. The triptolide (TP) is a kind of natural anti-tumor drug with a world patent, but its target and mechanism are yet not known. Objective: The study aims to explore and predict the target and mechanism of TP on non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CC) through network pharmacology technology. Methods: We screened the core targets of TP with NSCLC, PC and CC, respectively, and carried out network analysis, enrichment analysis and ligand-receptor docking to clarify its potential pharmacological mechanism. Results: By screening the core genes between TP with NSCLC, PC and CC, respectively, it was found that PTGS2 was the common target gene in the three cancers. NSCLC, CCL2, IL6, HMOX1 and COL1A1 are the specific target genes, while MMP2, JUN, and CXCL8 are the specific target genes in PC. In CC, the specific target genes includeERBB2, VEGFA, STAT1 andMAPK8. In enrichment analysis, it was found that the NF- κB, toll-like receptors and IL-17 signaling pathway were mainly involved in TP for these cancers. The binding energy of TP to the core target is less than that of cyclophosphamide. Conclusions: This study preliminarily revealed that TP may prevent and treat cancers\ through multiple targets and pathways. The possible mechanisms of TP include regulating immune and inflammatory responses, promoting apoptosis and inhibiting tumor development. It shows that TP may have a potential in treating kinds of tumors.

Network pharmacology and molecular docking approaches to investigating the mechanism of action of Zanthoxylum bungeanum in the treatment of oxidative stress-induced diseases

2020 ◽  
Vol 23 ◽  
Author(s):  
Rong Zhao ◽  
Meng-Meng Zhang ◽  
Dan Wang ◽  
Wei Peng ◽  
Qing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Components ◽  
Active Compounds ◽  
Zanthoxylum Bungeanum

Background: Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and its related mechanisms are still not systematically reported. Objective: The current study was aimed to explore the main active ingredients and its molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation. Methods: The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology. Results: A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGERAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities. Conclusion: The findings of this study not only indicate the main mechanisms involving in the oxidative stress-induced diseases, but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.

scholarly journals Network Pharmacology Reveals the Molecular Mechanism of Cuyuxunxi Prescription in Promoting Wound Healing in Patients with Anal Fistula

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yin Qu ◽  
Zhijun Zhang ◽  
Yafeng Lu ◽  
De Zheng ◽  
Yang Wei
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Target Genes ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Surgical Wound ◽  
Active Compounds

Background. The healing process of the surgical wound of anal fistulotomy is much slower because of the presence of stool within the wound. Cuyuxunxi (CYXX) prescription is a Chinese herbal fumigant that is being used to wash surgical wound after anal fistulotomy. This study aimed at investigating the molecular mechanism of CYXX prescription using a network pharmacology-based strategy. Materials and Methods. The active compounds in each herbal medicine were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and in Traditional Chinese Medicine Integrated Database (TCMID) analysis platform based on the criteria of oral bioavailability ≥40% and drug-likeness ≥0.2. The disease-related target genes were extracted from the Comparative Toxicogenomics Database. Protein-protein interaction network was built for the overlapped genes as well as functional enrichment analysis. Finally, an ingredient-target genes-pathway network was built by integrating all information. Results. A total of 375 chemical ingredients of the 5 main herbal medicines in CYXX prescription were retrieved from TCMSP database and TCMID. Among the 375 chemical ingredients, 59 were active compounds. Besides, 325 target genes for 16 active compounds in 3 herbal medicines were obtained. Functional enrichment analysis revealed that these overlapped genes were significantly related with immune response, biosynthesis of antibiotics, and complement and coagulation cascades. A comprehensive network which contains 133 nodes (8 disease nodes, 3 drug nodes, 8 ingredients, 103 target gene nodes, 7 GO nodes, and 4 pathway nodes) was built. Conclusion. The network built in this study might aid in understanding the action mechanism of CYXX prescription at molecular level to pathway level.

scholarly journals A network pharmacology perspective for deciphering potential mechanisms of action of Solanum nigrum L. in bladder cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Dong ◽  
Lin Hao ◽  
Kun Fang ◽  
Xiao-xiao Han ◽  
Hui Yu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Target Genes ◽  
Mendelian Inheritance ◽  
Solanum Nigrum ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Systematic Analysis ◽  
Ppi Networks ◽  
Therapeutic Benefits ◽  
Go Terms

Abstract Background Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. Methods Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I–T) and protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. Results Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. Conclusions S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

scholarly journals Network Pharmacology-Based Approach to Investigate the Mechanisms of Mahai Capsules in the Treatment of Cardiovascular Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Minjuan Shi ◽  
Bo Li ◽  
Qiuzhen Yuan ◽  
Xuefeng Gan ◽  
Xiao Ren ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Life Quality ◽  
Enrichment Analysis ◽  
Basic Research ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Target Disease ◽  
Compound Target

Background. Mahai capsules (MHC) have been deemed to be an effective herb combination for treatment of cardiovascular diseases (CVD) development and improvement of the life quality of CVD patients. To systematically explore the mechanisms of MHC in CVD, a network pharmacology approach mainly comprising target prediction, network construction, biological process and pathway analysis, and related diseases was adopted in this study. Methods. We collected the bioactive compounds and potential targets of MHC through the TCMSP servers. Candidate targets related to CVD were collected from Therapeutic Targets Database and PharmGkb database and analyzed using ClueGO plugin in Cytoscape. KEGG pathway was enriched and analyzed through the EnrichR platform, and protein-protein interaction networks were calculated by STRING platform. The compound-target, target-disease, and compound-target-disease networks were constructed using Cytoscape. Results. A total of 303 targets of the 57 active ingredients in MHC were obtained. The network analysis showed that PTGS2, PTGS1, HSP90, Scn1a, estrogen receptor, calmodulin, and thrombin were identified as key targets of MHC in the treatment of CVD. The functional enrichment analysis indicated that MHC probably produced the therapeutic effects against CVD by synergistically regulating many biological pathways, such as PI3K-Akt, TNF, HIF-1, FoxO, apoptosis, calcium, T-cell receptor, VEGF, and NF-kappa B signaling pathway. Conclusions. In summary, the analysis of the complete profile of the pharmacological properties, as well as the elucidation of targets, networks, and pathways, can further illuminate that the underlying mechanisms of MHC in CVD might be strongly associated with its synergic regulation of inflammation, apoptosis, and immune function, and provide new clues for its future development of therapeutic strategies and basic research.

scholarly journals Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 and SARS Mechanism of Fufang Banlangen Keli

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098842
Author(s):  
Li Cheng ◽  
Fei Wang ◽  
Shun Bo Zhang ◽  
Qiu Yun You
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Docking Studies ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Active Components

Purpose Fufang Banlangen Keli (FBK) has been recommended for its clinical treatment of Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS), but the mechanism of action is unclear. So, using network pharmacology and molecular docking, we studied the active components and mechanism of FBK in the treatment of COVID-19 and SARS. Methods The Encyclopedia of Traditional Chinese Medicine and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to screen the active components by oral bioactivity and drug likeness. Then, PharmMapper and SwissTargetPrediction databases were used to screen potential target genes of active components; the related target genes of COVID-19 and SARS were obtained from the GeneCards database. The intersection of the active components and disease-related targets was performed by the Venny2.1.0 database. The DAVID6.8 database and KOBAS3.0 database were used to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. The “components-targets-pathways (C-T-P)” network of FBK was conducted by Cytoscape3.6.1 software. The top active components, angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 3 Cl, were imported into AutoDock and PyMOL for molecular docking. Results From the FBK, a total of 28 active components and 73 gene targets were screened through network pharmacology. Twenty pathways were analyzed, including pathways in cancer, nod-like receptor signaling pathway, and pancreatic cancer, etc. ( P < 0.05). A total of 337 items were obtained by GO functional enrichment analysis ( P < 0.05), including 257 items for biological process, 38 items for cell composition, and 42 items for molecular function. Furthermore, molecular docking studies were performed to study potential binding between the key gene targets and selected active components. Conclusion Based on network pharmacology and molecular docking technology, qingdainone, (2Z)-2-(2-oxoindolin-3-ylidene) indolin-3-one, sinensetin, and acacetin in FBK were verified to bind to ACE2 and SARS-COV-2 3 Cl, so as to treat COVID-19 and SARS.

scholarly journals Mechanisms Underlying the Action of Ziziphi Spinosae Semen in the Treatment of Insomnia: A Study Involving Network Pharmacology and Experimental Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenhua Bian ◽  
Wenming Zhang ◽  
Jingyue Tang ◽  
Qianqian Fei ◽  
Minmin Hu ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Immunohistochemical Analysis ◽  
Functional Enrichment ◽  
Morphological Observation ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Gabaergic Synapse ◽  
Pentobarbital Sodium

Purpose: This study aimed to investigate the potential mechanisms and related bioactive components of ZSS for the treatment of insomnia.Method: The insomnia model of rat induced by PCPA was established. After oral administration of ZSS extract, the general morphological observation, pentobarbital sodium-induced sleep test and histopathological evaluation were carried out. Network pharmacology, assisted by UHPLC-Q-Exactive-MS/MS analysis, was developed to identify the targets of ZSS in the treatment of insomnia, as well as the corresponding signaling pathways. In addition, we validated the identified targets and pathways by RT-qPCR and immunohistochemical analysis.Results: The pentobarbital sodium-induced sleep test, determination of 5-HT and GABA levles in hypothalamic tissues and HE staining showed that ZSS extract was an effective treatment for insomnia. Network pharmacology analysis identified a total of 19 candidate bioactive ingredients in ZSS extract, along with 433 potentially related targets. Next, we performed protein-protein interaction (PPI), MCODE clustering analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and ingredient-target-pathway (I-T-P) sub-networks analysis. These methods allowed us to investigate the synergistic therapeutic effects of crucial pathways, including the serotonergic and GABAergic synapse pathways. Our analyses revealed that palmitic acid, coclaurine, jujuboside A, N-nornuciferine, caaverine, magnoflorine, jujuboside B, and betulinic acid, all played key roles in the regulation of these crucial pathways. Finally, we used the PCPA-induced insomnia in rats to validate the data generated by network pharmacology; these in vivo experiments clearly showed that pathways associated with the serotonergic and GABAergic system were activated in the rats model. Furthermore, ZSS treatment significantly suppressed high levels of HTR1A, GABRA1, and GABRG2 expression in the hypothalamus and reduced the expression levels of HTR2A.Conclusion: Based on the combination of comprehensive network pharmacology and in vivo experiments, we successfully identified the potential pharmacological mechanisms underlying the action of ZSS in the treatment of insomnia. The results provide a theoretical basis for further development and utilization of ZSS, and also provide support for the development of innovative drugs for the treatment of insomnia.

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