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.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanni Lai ◽  
Qiong Zhang ◽  
Haishan Long ◽  
Tiantian Han ◽  
Geng Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
New Drugs ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Components ◽  
Compound Screening

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

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.

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.

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.

A Network Pharmacology Analysis of the Systems-Perspective Anticancer Mechanisms of the Herbal Drug FDY2004 for Breast Cancer

2021 ◽  
Vol 16 (10) ◽  
pp. 1934578X2110491
Author(s):  
Ho-Sung Lee ◽  
In-Hee Lee ◽  
Kyungrae Kang ◽  
Sang-In Park ◽  
Tae-Wook Kwon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Herbal Drugs ◽  
Apoptosis Pathway ◽  
Anticancer Properties ◽  
Systems Perspective

Breast cancer is a malignant tumor with high incidence, prevalence, and mortality rates in women. In recent years, herbal drugs have been assessed as anticancer therapy against breast cancer, owing to their promising therapeutic effects and reduced toxicity. However, their pharmacological mechanisms have not been fully explored at the systemic level. Here, we conducted a network pharmacology analysis of the systems-perspective molecular mechanisms of FDY2004, an anticancer herbal formula that consists of Moutan Radicis Cortex, Persicae Semen , and Rhei Radix et Rhizoma, against breast cancer. We determined that FDY2004 may contain 28 active compounds that exert pharmacological effects by targeting 113 breast cancer-related human genes/proteins. Based on the gene ontology terms, the FDY2004 targets were involved in modulating biological processes such as cell growth, cell proliferation, and apoptosis. Pathway enrichment analysis identified various breast cancer-associated pathways that may mediate the anticancer activity of FDY2004, including the PI3K-Akt, MAPK, TNF, HIF-1, focal adhesion, estrogen, ErbB, NF-kappa B, p53, and VEGF signaling pathways. Thus, our analysis offers novel insights into the anticancer properties of herbal drugs for breast cancer treatment from a systemic perspective.

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 A Network Pharmacology Analysis to Explore the Effect ofAstragali Radix-Radix Angelica Sinensison Traumatic Brain Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Genggeng Xie ◽  
Weijun Peng ◽  
Pengfei Li ◽  
Zian Xia ◽  
Yuanyuan Zhong ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Experiment ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Neurological Deficits ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Go Annotation

Traumatic brain injury (TBI) is a critical public health and socioeconomic problem worldwide. The herb pairAstragali Radix(AR)-Radix Angelica Sinensis(RAS) is a common prescribed herbal formula or is added to other Chinese medicine prescriptions for traumatic brain injury (TBI) treatment. However, the underlying mechanisms are unclear. In this study, we aimed to explore the active ingredients and action targets of AR-RAS based on the combined methods of network pharmacology prediction and experimental verification. Furthermore, the corresponding potential mechanisms of “multicomponents, multitargets, and multipathways” were disclosed.Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) filter analysis, target prediction, known therapeutic targets collection, Gene Ontology (GO), pathway enrichment analysis, and network construction was used in this study. Further verification experiments were performed to reveal the therapeutic effects of AR-RAS in a rat model of TBI.Results. The comprehensive systematic approach was to successfully identify 14 bioactive ingredients in AR-RAS, while 33 potential targets hit by these ingredients related to TBI. Based on GO annotation analysis, multiple biological processes were significantly regulated by AR-RAS. In addition, 89 novel signaling pathways (P<0.05) underlying the effects of AR-RAS for TBI treatment were identified by DAVID. The neurotrophin signaling pathway was suggested as the major related pathway targeted by AR-RAS to improve axonal growth. The animal experiment confirmed that AR-RAS significantly induced tissue recovery and improved neurological deficits on the 14th day (P<0.01). Treatment with AR-RAS markedly reduced the protein and mRNA expression level of NogoA in the hippocampus of TBI rats.Conclusion. Our work illuminates the “multicompounds, multitargets, and multipathways” curative action of AR-RAS in the treatment of TBI by network pharmacology. The animal experiment verifies the effects of AR-RAS on neurological function improvement and axonal outgrowth via downregulation of NogoA expression, providing a theoretical basis for further research on treatment of TBI.

scholarly journals Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xiaoqin Ma ◽  
Meixiang Yu ◽  
Chenxia Hao ◽  
Wanhua Yang
Keyword(s):  
Molecular Docking ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Human Phenotype ◽  
Herbal Mixture ◽  
Relationship Of

Shuangbai Tablets (SBT), a traditional herbal mixture, has shown substantial clinical efficacy. However, a systematic mechanism of its active ingredients and pharmacological mechanisms of action against proteinuria continues being lacking. A network pharmacology approach was effectual in discovering the relationship of multiple ingredients and targets of the herbal mixture. This study aimed to identify key targets, major active ingredients, and pathways of SBT against proteinuria by network pharmacology approach combined with thin layer chromatography (TLC). Human phenotype (HP) disease analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking were used in this study. To this end, a total of 48 candidate targets of 118 active ingredients of SBT were identified. Network analysis showed PTGS2, ESR1, and NOS2 to be the three key targets, and beta-sitosterol, quercetin, and berberine were the three major active ingredients; among them one of the major active ingredients, quercetin, was discriminated by TLC. These results of the functional enrichment analysis indicated that the most relevant disease including these 48 candidate proteins is proteinuria, SBT treated proteinuria by sympathetically regulating multiple biological pathways, such as the HIF-1, RAS, AGE-RAGE, and VEGF signaling pathways. Additionally, molecular docking validation suggested that major active ingredients of SBT were capable of binding to HIF-1A and VEGFA of the main pathways. Consequently, key targets, major active ingredients, and pathways based on data analysis of SBT against proteinuria were systematically identified confirming its utility and providing a new drug against proteinuria.

scholarly journals Analysis of Molecular Mechanism of Erxian Decoction in Treating Osteoporosis Based on Formula Optimization Model

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Lang Yang ◽  
Liuyi Fan ◽  
Kexin Wang ◽  
Yupeng Chen ◽  
Lan Liang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Osteoclast Differentiation ◽  
Antibody Therapy ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Mechanism Analysis ◽  
Erxian Decoction

Osteoporosis (OP) is a highly prevalent orthopedic condition in postmenopausal women and the elderly. Currently, OP treatments mainly include bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) antibody therapy, selective estrogen receptor modulators, teriparatide (PTH1-34), and menopausal hormone therapy. However, increasing evidence has indicated these treatments may exert serious side effects. In recent years, Traditional Chinese Medicine (TCM) has become popular for treating orthopedic disorders. Erxian Decoction (EXD) is widely used for the clinical treatment of OP, but its underlying molecular mechanisms are unclear thanks to its multiple components and multiple target features. In this research, we designed a network pharmacology method, which used a novel node importance calculation model to identify critical response networks (CRNs) and effective proteins. Based on these proteins, a target coverage contribution (TCC) model was designed to infer a core active component group (CACG). This approach decoded the mechanisms underpinning EXD’s role in OP therapy. Our data indicated that the drug response network mediated by the CACG effectively retained information of the component-target (C-T) network of pathogenic genes. Functional pathway enrichment analysis showed that EXD exerted therapeutic effects toward OP by targeting PI3K-Akt signaling (hsa04151), calcium signaling (hsa04020), apoptosis (hsa04210), estrogen signaling (hsa04915), and osteoclast differentiation (hsa04380) via JNK, AKT, and ERK. Our method furnishes a feasible methodological strategy for formula optimization and mechanism analysis and also supplies a reference scheme for the secondary development of the TCM formula.

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