TCMSP: a database of systems pharmacology for drug discovery from herbal medicines.

Threatened abortion (TA) is a common complication with high incidence in the first trimester of pregnancy, which will end in miscarriage if not treated properly. The Chinese herbs Cuscutae Semen (Tusizi in Chinese) and Herba Taxilli (Sangjisheng in Chinese) first recorded in the ancient classic medical book Shennong Bencao Jing are effective and widely used as an herb pair for the treatment of TA, while the active ingredients and the functional mechanism of Tusizi-Sangjisheng herb pair treating TA are still unknown. In order to exploit the relationship between those two herbs and TA, systems pharmacology analysis was carried out in this study. A total of 75 ingredients of Tusizi-Sangjisheng were collected from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). 12 bioactive compounds were screened, and 153 directly related targets were predicted by systematic models. Besides, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to systematically explore the potential mechanisms of Tusizi-Sangjisheng treating TA. Meanwhile, Compound-Target (C-T), Target-Disease (T-D), and Target-Pathway (T-P) networks were constructed to further quest the underlying functional mechanisms of Tusizi-Sangjisheng. As a result, 31 targets and 3 key pathways were found to be directly related to TA that includes mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt), and transforming growth factor-β (TGF-β) signaling pathways. The results in this study may provide some valuable clues about the molecular mechanisms of the efficient Chinese herb pair Tusizi-Sangjisheng in the treatment of TA.

Traditional medicine believes that hypertrophic scar (HS) falls into the category of "blood stasis". Chinese herbs for promoting blood circulation and removing blood stasis, activating meridians, and relieving pain are usually selected to treat HS by traditional Chinese medicine (TCM). Both Semen Persicae (SP) and Flos Carthami (FC) are confirmed to be effective for HS. Clinically, SP and FC are often used in combination with each other. However, the pharmacodynamic mechanism and molecular target of SP-FC in the treatment of HS are still unclear. Therefore, this study is intended to explore the mechanism and target of SP-FC in the treatment of HS through network pharmacology combined with invitro cell and molecular biology experiments. Target genes of SP-FC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and targets of HS-related diseases were searched from databases such as Disgenet and GeneCards. Based on the targets searched and obtained, a Venn diagram was plotted to acquire common targets of SP-FC-HS. Next, STRING 11.0 was employed for protein-protein interaction (PPI) network analysis of common targets; and cytoscape 3.9.0 for connection relationship analysis of PPI and plotting of a "drug-component-target" network diagram. Besides, a modified explant culture method was applied to separate primary hypertrophic scar fibroblasts (HSFs); MTT assay to detect cell viability of HSFs after treatment by SP-FC for 24 h; Annexin V-FITC/PI double staining combined with flow cytometry to test apoptosis; western blot to check the protein expression level of p53; and real-time fluorescence quantitative PCR to determine mRNA level of p53. In the analysis of network pharmacology, 269 pharmacological targets of SP, 449 pharmacological targets of FC, and 2569 targets of HS-related diseases were screened from the databases. After plotting the Venn diagram, 116 common targets of SP-FC-HS were acquired. In vitro experiments showed that the expression of p53 in HSFs was decreased. SP-FC significantly reduces the viability of HSFs, increases p53 levels in HSFs, and promotes apoptosis. SP-FC can reduce scar formation by promoting p53 expression.

Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study

Network Pharmacology-based Analysis on the Molecular Biological Mechanisms of Xin Hui Tong Formula in Coronary Heart Disease Treatment

BackgroundCoptis chinensis, a prominent herb in traditional Chinese medicine, is widely utilized for its therapeutic effects against Streptococcus infections, though its precise mechanisms of action remain insufficiently understood. This study aims to clarify the potential mechanisms and active compounds of C. chinensis in the treatment of Streptococcus.MethodsActive compounds of C. chinensis were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and their potential targets were predicted from multiple public resources. These targets were intersected with streptococcus-related genes to identify overlapping targets, which were then used to construct a protein–protein interaction (PPI) network and screen for key hub genes. To investigate the pharmacological mechanisms, Gene Ontology and KEGG pathway enrichment analyses were performed. Molecular docking was employed to evaluate the binding affinities between active compounds and core target proteins, followed by molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations to assess binding stability and free energy.ResultsA total of 24 active compounds were identified, along with 180 overlapping targets related to streptococcal infection. PPI network analysis revealed ten key hub genes, including IL1β, IL6, and MMP9. Enrichment analysis suggested that C. chinensis may inhibit the TLR4/NF-κB inflammatory pathway to modulate host immunity and mediate lipid metabolism reprogramming to restrict pathogen proliferation. Several core targets were also enriched in pathways related to extracellular matrix remodeling and immune regulation, indicating potential indirect effects on host–pathogen interface interactions. Molecular docking and simulation confirmed stable binding between major active ingredients and streptococcus-associated proteins.ConclusionThis study provides mechanistic insights into the multi-component, multi-target, and multi-pathway effects of C. chinensis against streptococcal infections. The findings offer a theoretical basis for future experimental validation and clinical translation.

See related article, pages 1973–1979. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines, for which extensive observational and anecdotal experience has accumulated over the past thousand years. The World Health Organization (WHO) defines traditional medicine as “health practices, approaches, knowledge and beliefs incorporating plant, animal and mineral based medicines, spiritual therapies, manual techniques and exercises, applied singularly or in combination to treat, diagnose and prevent illnesses or maintain well-being”.1 Unlike Western medicine, which focuses on disease, traditional medicine takes the approach that the body provides external clues to an internal imbalance that can be addressed by interventions such as herbs and acupuncture (holistic treatment approach).2 According to a 2003 WHO report,1 traditional medicine is very popular in all developing countries, and its use is rapidly increasing in industrialized countries. For example, traditional herbal preparations account for 30% to 50% of the total medicinal consumption in China. In Europe, North America and other industrialized regions, over 50% of the population have used traditional medicine at least once. The global market for herbal medicines currently stands at over US $60 billion annually and is growing steadily.1 In recent years, several reviews have been published on the effect and potential benefits of traditional Eastern medicine in stroke.3–7 It has been suggested that some herbal medicines, or their products, may improve microcirculation in the brain,4,8 protect against ischemic reperfusion injury,8,9 possess neuroprotective properties3,4 and inhibit apoptosis,10 thus justifying their use in ischemic stroke patients. However, unlike industrially manufactured pharmacological drugs used in Western medicine, the active (potent) components of herbal medicines often have not been specified and measured precisely, although there have been recent attempts to regulate dosages and use of …

BackgroundHuangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation.MethodsThe active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment’s central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation.ResultsA total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the α7 nicotinic acetylcholine receptor (α7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1β), interleukin 10 (IL-10) and growth factor beta (TGF-β1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD’s compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of α7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-β, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-β1.ConclusionHQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of α7 nAchR expression.

Network pharmacology (NP) is a useful, emerging means of understanding the complex pharmacological mechanisms of traditional herbal medicines. Sochehwan (SCH) is a candidate herbal prescription for drug repurposing as it has been suggested to have beneficial effects on metabolic syndrome. In this study, NP was adopted to complement the shortcomings of literature-based drug repurposing strategies in traditional herbal medicine. We conducted in vitro studies to confirm the effects of SCH on potential pharmacological targets identified by NP analysis. Herbal compounds and molecular targets of SCH were explored and screened from a traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and an oriental medicine advanced searching integrated system (OASIS). Forty-seven key targets selected from a protein-protein interaction (PPI) network were analyzed with gene ontology (GO) term enrichment and KEGG pathway enrichment analysis to identify relevant categories. The tumor necrosis factor (TNF) and mitogen-activated protein kinase (MAPK) signaling pathways were presented as significant signaling pathways with lowest p-values by NP analysis, which were downregulated by SCH treatment. The signal transducer and activator of transcription 3 (STAT3) was identified as a core key target by NP analysis, and its phosphorylation ratio was confirmed to be significantly suppressed by SCH. In conclusion, the NP-based approach used for target prediction and experimental data obtained from Raw 264.7 cells strongly suggested that SCH can attenuate inflammatory status by modulating the phosphorylation status of STAT3.

Natural products, including traditional herbal medicine (THM), are known to exert their therapeutic effects by acting on multiple targets, so researchers have employed network pharmacology methods to decipher the potential mechanisms of THM. To conduct THM-network pharmacology (THM-NP) studies, researchers have employed different tools and databases for constructing and analyzing herb–compound–target networks. In this study, we attempted to capture the methodological trends in THM-NP research. We identified the tools and databases employed to conduct THM-NP studies and visualized their combinatorial patterns. We also constructed co-author and affiliation networks to further understand how the methodologies are employed among researchers. The results showed that the number of THM-NP studies and employed databases/tools have been dramatically increased in the last decade, and there are characteristic patterns in combining methods of each analysis step in THM-NP studies. Overall, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was the most frequently employed network pharmacology database in THM-NP studies. Among the processes involved in THM-NP research, the methodology for constructing a compound–target network has shown the greatest change over time. In summary, our analysis describes comprehensive methodological trends and current ideas in research design for network pharmacology researchers.

Network pharmacology, a holistic approach based on the theory of biological network technology, integrates information from biological systems, drugs, and diseases. Here, this theory was used to predict the targets of Wu-Wei-Wen-Tong Chubi capsule (WWWT) to explore the mechanism in the treatment of rheumatoid arthritis (RA). The ingredients of each herbal medicine in WWWT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were screened through bioavailability (OB) ≥30% and drug-likeness (DL) ≥ 0.18. SwissTargetPrection and TCMSP were utilized to calculate and predict the targets of active ingredients. RA-related targets were obtained by searching the Genecards and OMIM databases. The common targets of RA and WWWT were used for gene ontology (GO), KEGG pathway enrichment, protein-protein interaction (PPI) analysis, and molecular docking. And then, four key genes were screened for subsequent verification experiments. In total, 90 active compounds and 330 potential targets of WWWT, 1310 targets of RA, and 135 intersection targets were found. Additionally, GO and pathway analysis identified 4610 significant GO terms and 147 significant KEGG pathways. Based on the PPI network, 11 key genes including IL-6, MMP-9, and TNF-α were screened out for molecular docking. Molecular docking showed that these key genes have good binding activities to active compounds of WWWT such as oroxylin a, kaempferol, and luteolin. Simultaneously, Western blot experimental validation demonstrated that the protein expressions of IL-6, MMP-9, TNF-α, and VEGFA significantly decreased after WWWT treatment. The mechanism of WWWT in treating RA involves multiple active compounds acting on multiple targets, and multiple pathways, which provides an important reference for further elucidation the mechanism and clinical applications of WWWT in the treatment of RA.

Aims of this studyThis study aims to investigate the potential of Huangqin Tang (HQT), a traditional Chinese medicine formulation, in the treatment of breast cancer (BC) through a comprehensive approach integrating network pharmacology, molecular docking, and experimental validation.MethodsChemical composition and target information of HQT were collected using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related target genes were obtained from the GeneCards database. Network pharmacological analysis, including construction of compound-disease-target networks and protein-protein interaction networks, was performed. Molecular docking simulations were conducted to evaluate the binding affinity between HQT components and key targets. Experimental validation was carried out using cell viability assays, clone formation assays, flow cytometry, Western blotting, and pathway analysis.ResultsA total of 210 candidate targets were identified. Network analysis revealed STAT3, AKT1, MAPK3 etc. as central targets. Enrichment analysis suggested HQT may exert anti-tumor effects through regulating lipid metabolism and inflammation related pathways. Molecular docking showed that the key compounds baicalein, wogonin, kaempferol and quercetin all bound effectively to MAPK1. The binding of baicalein to IL6 and naringenin to TNF-α was also relatively stable. The experimental results demonstrated that HQT effectively inhibited the proliferation of breast cancer cells, with IC50 values of 2.334 mg/mL and 1.749 mg/mL in MCF-7 cells at 24 h and 48 h, and IC50 values of 1.286 mg/mL and 1.496 mg/mL in MDA-MB-231 cells at 24 h and 48 h, respectively. Furthermore, HQT induced cell cycle arrest at the G2/M phase in breast cancer cells and downregulated the expression of related proteins including CDK1, Cyclin B1, CDK2, and Cyclin E. Additionally, HQT promoted apoptosis in breast cancer cells by upregulating the expression of Bak and CC-3, while downregulating the expression of Bcl-2. Notably, HQT also exhibited regulatory effects on the HIF-1 signaling pathway.ConclusionsThis study provides insights into the potential multi-component and multi-target mechanisms of HQT against BC, suggesting it may achieve therapeutic effects through regulating inflammatory response and cancer-related pathways via the identified active compounds and targets. The findings highlight the importance of integrating traditional medicine with modern approaches for the development of novel cancer therapies.

Background Hyssopus cuspidatus Boriss. (Shen Xiang Cao (SXC)), a traditional medicine herb in Xinjiang, has a long history of being used by minorities to treat asthma. However, its active antiasthmatic compounds and underlying mechanism of action are still unknown. The aim of this study was to investigate the bioactive compounds and explore the molecular mechanism of SCX in the treatment of asthma using network pharmacology. Methods The compounds of SCX were collected by a literature search, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction were used to predict targets and screen active compounds. Moreover, asthma-related targets were obtained based on DisGeNET, Herb, and GeneCards databases, and a protein-protein interaction (PPI) network was built by the STRING database. Furthermore, the topological analysis of the PPI and SXC-compound-target networks were analyzed and established by Cytoscape software. Finally, the RStudio software package was used for carrying out Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. AutoDock tools and AutoDock Vina were used to molecularly dock the active compounds and key targets. Results A total of 8 active compounds and 258 potential targets related to SXC were predicted, and PPI network screened out key targets, including IL-6, JUN, TNF, IL10, and CXCL8. GO enrichment analysis involved cell responses to reactive oxygen species, oxidative stress, chemical stress, etc. In addition, KEGG pathway analysis showed that SXC effectively treated asthma through regulation of mitogen-activated protein kinases (MAPK) signaling pathways, interleukin 17 (IL-17) signaling pathways, toll-like receptor (TLR) signaling pathways, and tumor necrosis factor (TNF) signaling pathways. Conclusion The preliminary study that was based on multiple compounds, multiple targets, and multiple pathways provides a scientific basis for further elucidating the molecules involved and the underlying antiasthma-related mechanisms of SXC.

The purpose of this study is to investigate the ingredients and mechanisms through which Dalbergiae Odoriferae Lignum (DOL) reduces adriamycin-induced cardiotoxicity. DOL's ingredients and drug targets were acquired from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and adriamycin-induced cardiotoxicity disease targets were gathered from GeneCards and National Center for Biotechnology Information (NCBI). The therapeutic targets of DOL against adriamycin-induced cardiotoxicity were identified by intersecting drug and disease targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using R. Subsequently, core targets were determined and used for molecular docking with DOL ingredients. In vitro and in vivo experiments validated DOL's primary ingredients against adriamycin-induced cardiotoxicity efficacy. Western blot and immunohistochemistry verified its impact on target protein. After intersecting 530 drug targets and 51 disease targets, 19 therapeutic targets for DOL alleviated adriamycin-induced cardiotoxicity were received. Molecular docking demonstrated that DOL primary ingredient formononetin had a robust binding affinity for nitric oxide synthase 3 (NOS3). Experimental results showed that formononetin effectively mitigated adriamycin-induced cardiotoxicity. Additionally, western blot and immunohistochemistry showed that formononetin improved NOS3 expression. The network pharmacology and experimentation suggest that the primary ingredient of DOL, formononetin, may target NOS3 to act as a therapeutic agent for adriamycin-induced cardiotoxicity.

Objective Our objective was to analyze the traditional Chinese medicine (TCM) syndrome and treatment laws of diabetic kidney disease (DKD) and the action mechanism of high-frequency Chinese herbs in the treatment of DKD based on real-world study. Methods The data of patients with DKD who had been treated in the First Hospital Affiliated to Henan University of Chinese Medicine from January 1, 2014 to December 31, 2021 were retrospectively analyzed through the hospital information management system. The contents of the cases were statistically analyzed using IBM SPSS Statistics 25 software, and the laws of DKD treatment were summarized. Network pharmacology and molecular docking were used to analyze the action mechanism of high-frequency Chinese herbs in the treatment of DKD. Results The data of a total of 1,201 patients with DKD were included, involving 72 kinds of TCM syndromes. Nine disease nature elements and six disease location elements were extracted, involving 405 Chinese herbs. The top five high-frequency Chinese herbs were Baizhu (Atractylodis Macrocephalae Rhizoma), Fuling (Poria), Huangqi (Astragali Radix), Chuanxiong (Chuanxiong Rhizoma), and Danshen (Salviae Miltiorrhizae Radix et Rhizoma). Thirty kinds of Chinese herbs with the frequency of ≥100 were mainly deficiency-tonifying herbs and blood-activating and stasis-eliminating herbs. The medicinal properties were mainly warm and mild, and the medicinal flavors were sweet and bitter mostly. For the meridian tropism, the main meridian tropism of these herbs is spleen meridian and lung meridian. The clustering method aggregated the 30 commonly used Chinese herbs into six categories. A total of 58 effective active ingredients of high-frequency Chinese herbs and 164 related targets were screened based on the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); 1,434 targets of DKD and 90 potential targets of high-frequency Chinese herbs for DKD were obtained. “Active ingredient-potential target” network topology analysis indicated that quercetin, luteolin, 7-O-methylisoxitol, hederagenin, and 4-methylene miltirone were the five core chemical components of high-frequency Chinese herbs in the treatment of DKD. Protein–protein interaction network topology analysis indicated that protein kinase B1, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, tumor protein P53 were the core protein targets. Twenty signaling pathways were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Molecular docking showed that luteolin, 4-methylene miltirone, and osthole had strong binding to AKT1. Conclusion The differentiation and treatment of DKD with TCM follows the principles of “taking kidney as the root, considering both the liver and spleen, tonifying qi and nourishing yin, promoting blood circulation and resolving blood stasis.” High-frequency Chinese herbs for the treatment of DKD have multicomponent, multitarget, and multipath characteristics.

In this study, network pharmacology and molecular docking technology were used to explore the molecular mechanisms of the Duhuo Jisheng decoction in the treatment of osteoarthritis (OA). The chemical composition of the prescriptions was obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database and the retrieved literature. Targets for the active ingredients were obtained using TCMSP and the Swiss Target Prediction Database. Disease targets were obtained from GeneCards and DisGeNET databases. The online tool, Venny, was used to obtain common targets for drugs and diseases. Protein-protein interactions (PPI) between common targets were analyzed using the search tool for the retrieval of interacting genes/proteins (STRING) database. Common targets were analyzed for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking of the first 10 targets and first 10 components was verified using AutoDock Tools software, and the docking diagram was visualized using PyMOL software. After screening, 210 chemical components of the Duhuo Jisheng decoction (DHJSD) were identified. The 253 common targets of drugs and diseases were combined by eliminating repeat values. Based on PPI network analysis, the top ten targets were SRC, STAT3, MAPK3, MAPK1, RELA, PIK3R1, HSP90AA1, TP53, EP300, and AKT1. KEGG analysis showed that DHJSD could regulate the HIF-1, PI3K-Akt, and JAK-STAT signaling pathways. The biological processes involved include inflammatory reactions, the negative regulation of apoptosis, and the positive regulation of cell proliferation. Molecular docking results showed that all targets, except the RELA protein, showed good binding to the compounds, indicating that the 10 components might exert therapeutic effects by binding to the above targets. DHJSD can treat OA by regulating the HIF-1, PI3K-Akt, and JAK-STAT signaling pathways. The proteins involved were SRC, STAT3, MAPK3, MAPK1, and PIK3R1. In this study, network pharmacology was used to predict the mechanism of DHJSD in OA treatment, which was verified by molecular docking to provide experimental research ideas and scientific basis for OA treatment.