Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Gegen Qinlian Decoction for Rotavirus Enteritis

Ethnopharmacological Relevance. Gegen Qinlian decoction (GGQLD) is an effective formula treatment for rotavirus enteritis (RVE), which has been applied for 1900 years. It consists of 4 herbal medicines corresponding to the four roles “monarch, minister, assistant, and guide,” which is the basic rule of prescription composition in traditional Chinese medicine (TCM). However, its active ingredients and therapeutic mechanism on RVE have not been fully investigated. Materials and Methods. In this study, a network pharmacology-based strategy was used to elucidate the mechanism of GGQLD for the treatment of RVE. Oral bioavailability and drug-likeness were taken as the judgment criteria to search the active ingredients of GGQLD in traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The affinity between protein and ingredients was further determined using the similarity ensemble approach to find the corresponding targets. According to the genes related to enteritis in GeneCards database, the key targets were screened by intersections between drug and disease targets. And the therapeutic mechanism was predicted using the protein-protein interactions (PPIs), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which was verified by detecting calcium ion concentration with the fluorescent probe. Result. 130 active ingredients were screened from GGQLD, including (R)-canadine, moupinamide, formononetin, and other flavonoids. They act on a total of 366 targets, which is mainly distributed in the biological process of hormone binding or signaling pathways of neuroactive ligand receptor interaction, serotonergic synapse, and calcium signaling pathway. Furthermore, serotonin receptors, adrenergic receptors, cholinergic receptors, and dopamine receptors in the enteric nervous system may be the key targets of RVE treatment by GGQLD. Conclusion. This study demonstrated that the potential mechanism that GGQLD can effectively improve the symptoms of RVE may depend on the regulation of calcium ions, serotonin, and gastrointestinal hormone ion that could mutually affect the intestinal nervous system.

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Mode of Action of Shan-Zhu-Yu (Cornus officinalis Sieb. et Zucc.) in the Treatment of Depression Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8838888 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Ping Liu ◽

Ping Yang ◽

Lan Zhang

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

G Protein ◽

Caspase 3 ◽

Target Genes ◽

Network Pharmacology ◽

Receptor Interaction ◽

Active Ingredients ◽

Treatment Of Depression ◽

G Protein Coupled

Background. Although the traditional Chinese medicine Shan-Zhu-Yu may be efficacious against depression, its mechanism of action is unknown. In this study, we aimed to explore the possible mechanisms of action of Shan-Zhu-Yu in the treatment of depression using network pharmacology. Methods. The active ingredients and targets of Shan-Zhu-Yu were obtained from the Traditional Chinese Medicine System Pharmacology Database (TCMSP) database and converted into gene names using UniProt. Then, the target genes of depression were collected using GeneCards and OMIM. Drug disease intersection genes were obtained using a Venn tool, and a protein-protein interaction network was constructed using STRING. Cytoscape was used to construct an active ingredients-targets-drug-disease network. GO and KEGG pathway enrichment analyses were performed using DAVID. Furthermore, Autodock was used to evaluate drug and target binding and explore possible molecular mechanisms. Results. We identified 9721 disease genes, 13 active ingredients, 50 target genes, and 48 drug disease intersecting genes. The results of the GO enrichment analysis suggested that Shan-Zhu-Yu affects the activity of G protein-coupled amine, neurotransmitter, steroid hormone, nuclear, and G protein-coupled neurotransmitter receptors in the treatment of depression by acting on hormone and nuclear receptor binding. The main signaling pathways were associated with neuroactive ligand-receptor interaction, calcium, cGMP-PKG, apoptosis, estrogen, p53, and AGE-RAGE. Molecular docking confirmed that the active components of Shan-Zhu-Yu (e.g., telocinobufagin and β-sitosterol) docked suitably with NR3C1, Bax, Bcl-2, and caspase-3. Shan-Zhu-Yu may exert its therapeutic effects on depression via multiple targets and pathways. Conclusions. The present study elucidates that Shan-Zhu-Yu suppresses the expression of Bax and caspase-3 and promotes that of NR3C1 and Bcl-2 through neuroactive ligand-receptor interaction and apoptosis signaling pathways. Therefore, Shan-Zhu-Yu is a potential treatment option for depression, and the results of this study will provide new reference points for future experimental research and a scientific basis for its widespread clinical application.

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A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

10.21203/rs.3.rs-90765/v1 ◽

2020 ◽

Author(s):

Ying Li ◽

Guhang Wei ◽

Zhenkun Zhuang ◽

Mingtai Chen ◽

Changjian Yuan ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components

Abstract BackgroundCorydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used.Materials and MethodsThe active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform.Results49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsOverall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

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A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

10.21203/rs.3.rs-41449/v1 ◽

2020 ◽

Author(s):

Ying Li ◽

Guhang Wei ◽

Zhenkun Zhuang ◽

Mingtai Chen ◽

Haidan Lin ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components

Abstract Background. Corydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used. Materials and Methods. The active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform. Results. 49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions. Overall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

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A network pharmacology study on the Cervix Prescription for treatment of Cervical Cancer

10.21203/rs.3.rs-835232/v1 ◽

2021 ◽

Author(s):

Pian Ying ◽

Yingping Zhu

Keyword(s):

Cervical Cancer ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Therapeutic Targets ◽

Interaction Network ◽

Research Direction ◽

Network Pharmacology ◽

Jiangxi Province ◽

Signal Pathways ◽

Active Ingredients

Abstract Purpose: Based on the method of network pharmacology to explore the mechanism of the Cervical Prescription(CP) in the treatment of cervical cancer(CC) . Methods: To obtain the active ingredients and potential targets of CP from the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP) ; To search for targets related to cervical cancer through the database, and map the CP and the targets; Screen the core Targets, a Chinese medicine compoundtarget network and STRING database was used to construct a protein-protein interaction network (PPI). The DAVID 6.8 online tool was used to perform gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses of overlapping targets. Results: The CP contains 2 active ingredients, corresponding to 301 non-reactive targets; 10 GO biological process related items and 73 signal pathways were obtained. Conclusion: By constructing a network diagram of "components-targets-pathways", 1Project fund: Zhejiang Provincial Natural Science Foundation Project(CN) (LQ20H270016); Zhejiang Traditional Chinese Medicine Administration (CN) (2020ZB087). *Profile of the author: Zhu Yingping, (1987-), female, attending physician, from Ganzhou, Jiangxi Province, master's degree student, research direction: Chinese medicine prevention and treatment of gynecological malignancies; E-mail: [email protected] this study revealed that CP can exert its efficacy through multiple components, multiple targets, and multiple pathways to achieve the purpose of preventing and treating CC.The network pharmacology-based approach in the present study showed promising potential for identifying the main therapeutic targets from TCM formulas. This study provides valuable information for TCM researchers and clinicians to better understand the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings.

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Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

BioData Mining ◽

10.1186/s13040-020-00225-8 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Ying Huang ◽

Wen-jiang Zheng ◽

Yong-shi Ni ◽

Mian-sha Li ◽

Jian-kun Chen ◽

...

Keyword(s):

Chinese Medicine ◽

Signaling Pathways ◽

Signaling Pathway ◽

Mapk Signaling ◽

Venn Diagram ◽

Network Pharmacology ◽

Active Ingredients ◽

Integrated Network ◽

Therapeutic Mechanism ◽

The World

Abstract Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

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Investigation on the Mechanism of Qubi Formula in Treating Psoriasis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4683254 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Lin Zhou ◽

Lingyun Zhang ◽

Disheng Tao

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Cellular Response ◽

Nuclear Translocation ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Core Network ◽

Active Ingredients ◽

Pharmacologically Active

Objective. To elucidate the pharmacological mechanisms of Qubi Formula (QBF), a traditional Chinese medicine (TCM) formula which has been demonstrated as an effective therapy for psoriasis in China. Methods. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, BATMAN-TCM database, and literature search were used to excavate the pharmacologically active ingredients of QBF and to predict the potential targets. Psoriasis-related targets were obtained from Therapeutic Target Database (TTD), DrugBank database (DBD), MalaCards database, and DisGeNET database. Then, we established the network concerning the interactions of potential targets of QBF with well-known psoriasis-related targets by using protein-protein interaction (PPI) data in String database. Afterwards, topological parameters (including DNMC, Degree, Closeness, and Betweenness) were calculated to excavate the core targets of Qubi Formula in treating psoriasis (main targets in the PPI network). Cytoscape was used to construct the ingredients-targets core network for Qubi Formula in treating psoriasis, and ClueGO was used to perform GO-BP and KEGG pathway enrichment analysis on these core targets. Results. The ingredient-target-disease core network of QBF in treating psoriasis was screened to contain 175 active ingredients, which corresponded to 27 core targets. Additionally, enrichment analysis suggested that targets of QBF in treating psoriasis were mainly clustered into multiple biological processes (associated with nuclear translocation of proteins, cellular response to multiple stimuli (immunoinflammatory factors, oxidative stress, and nutrient substance), lymphocyte activation, regulation of cyclase activity, cell-cell adhesion, and cell death) and related pathways (VEGF, JAK-STAT, TLRs, NF-κB, and lymphocyte differentiation-related pathways), indicating the underlying mechanisms of QBF on psoriasis. Conclusion. In this work, we have successfully illuminated that Qubi Formula could relieve a wide variety of pathological factors (such as inflammatory infiltration and abnormal angiogenesis) of psoriasis in a “multicompound, multitarget, and multipathway” manner by using network pharmacology. Moreover, our present outcomes might shed light on the further clinical application of QBF on psoriasis treatment.

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Network pharmacology evaluation of the active ingredients and potential targets of XiaoLuoWan for application to uterine fibroids

Bioscience Reports ◽

10.1042/bsr20202342 ◽

2020 ◽

Vol 40 (12) ◽

Author(s):

Yonghui Yu ◽

Fang Yang ◽

Hong Liu

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Calcium Signaling ◽

Signaling Pathway ◽

Uterine Fibroids ◽

Therapeutic Targets ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Ingredients ◽

Calcium Signaling Pathway

Abstract XiaoLuoWan (XLW) is a classical formula in traditional Chinese medicine (TCM) that has satisfactory therapeutic effects for uterine fibroids (UFs). However, its underlying mechanisms remain unclear. To elucidate the pharmacological actions of XLW in treating UFs, an ingredient–target–disease framework was proposed based on network pharmacology strategies. The active ingredients in XLW and their putative targets were obtained from the TCM systems pharmacology database and analysis platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) platforms. The known therapeutic targets of UFs were acquired from the DigSee and DrugBank databases. Then, the links between putative XLW targets and therapeutic UF targets were identified to establish interaction networks by Cytoscape. Finally, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of overlapping gene targets were performed in the STRING database and visualized in R software. In total, 9 active compounds were obtained from 74 ingredients, with 71 curative targets predicted in XLW. Moreover, 321 known therapeutic targets were closely related to UFs, with 29 targets overlapping with XLW and considered interacting genes. Pathway enrichment revealed that the calcium signaling pathway was significantly enriched and the mitogen-activated protein kinase (MAPK) signaling pathway, cAMP signaling pathway, cancer and vascular smooth muscle contraction pathways, cGMP-PKG signaling pathway, and AGE-RAGE signaling pathway were closely associated with XLW intervention for UFs. In conclusion, the network pharmacology detection identified 9 available chemicals as the active ingredients in XLW that may relieve UFs by regulating 29 target genes involved in the calcium signaling pathway, MAPK pathway and cAMP pathway. Network pharmacology analyses may provide more convincing evidence for the investigation of classical TCM prescriptions, such as XLW.

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Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

PLoS ONE ◽

10.1371/journal.pone.0252508 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252508

Author(s):

Jingyun Jin ◽

Bin Chen ◽

Xiangyang Zhan ◽

Zhiyi Zhou ◽

Hui Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathways ◽

Target Genes ◽

Network Pharmacology ◽

Signal Pathways ◽

Active Ingredients ◽

Molecular Docking Study

Background and objective We aimed to predict the targets and signal pathways of Xiao-Chai-Hu-Tang (XCHT) in the treatment of colorectal cancer (CRC) based on network pharmacology, just as well as to further analyze its anti-CRC material basis and mechanism of action. Methods We adopted Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) databases to screen the active ingredients and potential targets of XCHT. CRC-related targets were retrieved by analyzing published microarray data (accession number GSE110224) from the Gene Expression Omnibus (GEO) database. The common targets were used to construct the “herb-active ingredient-target” network using the Cytoscape 3.8.0 software. Next, we constructed and analyzed protein-to-protein interaction (PPI) using BisoGenet and CytoNCA plug-in in Cytoscape. We then performed Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes using the R package of clusterProfiler. Furthermore, we used the AutoDock Tools software to conduct molecular docking studies on the active ingredients and key targets to verify the network pharmacological analysis results. Results We identified a total of 71 active XCHT ingredients and 20 potential anti-CRC targets. The network analysis revealed quercetin, stigmasterol, kaempferol, baicalein, and acacetin as potential key compounds, and PTGS2, NR3C2, CA2, and MMP1 as potential key targets. The active ingredients of XCHT interacted with most CRC disease targets. We showed that XCHT’s therapeutic effect was attributed to its synergistic action (multi-compound, multi-target, and multi-pathway). Our GO enrichment analysis showed 46 GO entries, including 20 biological processes, 6 cellular components, and 20 molecular functions. We identified 11 KEGG signaling pathways, including the IL-17, TNF, Toll-like receptor, and NF-kappa B signaling pathways. Our results showed that XCHT could play a role in CRC treatment by regulating different signaling pathways. The molecular docking experiment confirmed the correlation between five core compounds (quercetin, stigmasterol, kaempferol, baicalein, and acacetin) just as well as PTGS2, NR3C2, CA2, and MMP1. Conclusion In this study, we described the potential active ingredients, possible targets, and key biological pathways responsible for the efficacy of XCHT in CRC treatment, providing a theoretical basis for further research.

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Antidepressant Mechanism of Traditional Chinese Medicine Formula Xiaoyaosan in CUMS-Induced Depressed Mouse Model via RIPK1-RIPK3-MLKL Mediated Necroptosis Based on Network Pharmacology Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.773562 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhi-Yi Yan ◽

Hai-Yan Jiao ◽

Jian-Bei Chen ◽

Kai-Wen Zhang ◽

Xi-Hong Wang ◽

...

Keyword(s):

Chinese Medicine ◽

Treatment Group ◽

Traditional Chinese Medicine ◽

Target Genes ◽

Network Pharmacology ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Active Ingredients ◽

Chinese Medicine Formula ◽

Treatment Of Depression

Background: Depression is a stress-related disorder that seriously threatens people’s physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders.Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan.Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the “botanical drugs-active ingredients-target genes” network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1β, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections.Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice.Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.

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Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis

10.21203/rs.3.rs-1176592/v1 ◽

2022 ◽

Author(s):

Lei Dang ◽

Chunbo Zhang ◽

Biru Su ◽

Ning Na ◽

Qiuling Huang ◽

...

Keyword(s):

Chinese Medicine ◽

Network Analysis ◽

Traditional Chinese Medicine ◽

Oral Administration ◽

Target Genes ◽

Steroid Hormone ◽

Network Pharmacology ◽

Receptor Interaction ◽

Hormone Biosynthesis ◽

Tof Ms

Abstract Background: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with ZSYT pills. However, the pharmacological mechanism of action of these pills remains unclear.Methods: The components of ZSYT found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of ZSYT pills. The potential targets of components were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and SwissTargetPrediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, therapeutic target database, and Genetic Association Database. The overlapping genes between the potential targets of ZSYT components and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.Results: Nineteen components in ZSYT pills were detected in the serum of POF mice after oral administration. A total of 695 ZSYT-related targets was screened, and 344 POF-related targets were collected. From the results of ZSYT-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with ZSYT pills. Moreover, the pathway enrichment results suggested that ZSYT pills treat POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.Conclusions: We demonstrated that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis are very likely to be therapeutic mechanism of ZSYT pills in treating POF. Our study suggests that combining the analysis of ZSYT pills components in blood in vivo in the POF models and network pharmacology prediction may offer a tool to characterize the mechanism of ZSYT pills in the POF.

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