Traditional Chinese Medicine Systems Pharmacology Database And Analysis Platform Research Articles

Widely targeted metabolomics analysis of Sanghuangporus vaninii mycelia and fruiting bodies at different harvest stages

Sanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.

Exploring the Mechanisms of Yuanhu Zhitong Oral Liquid for Primary Dysmenorrhea through Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Objective: Primary dysmenorrhea (PD) is a prevalent gynecological disorder. Yuanhu Zhitong oral liquid (YHZT) presents a promising alternative treatment for PD. However, the mechanisms underlying its efficacy remain unclear. This study aims to investigate the potential targets and mechanisms of action of YHZT in treating PD using network pharmacology, molecular docking, and molecular dynamics simulations. Methods: Potential compounds from YHZT were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Traditional Chinese Medicine Information Database (TCMID). The relevant targets of these compounds were identified using the similarity ensemble approach (SEA) and the Swiss Target Prediction database. PD-related targets were retrieved from the Genecards, DrugBank, and Disgenet databases. ClusterProfiler was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The compound-target-pathway (CTP) network was constructed to facilitate the identification of key compounds, core targets, and signaling pathways. Finally, molecular docking and molecular dynamics simulations were performed to evaluate the interactions between the targets and compounds. Results: A total of 153 putative compounds and 129 targets of YHZT were identified. Network topology analysis revealed eight core targets and six key compounds. The effects of YHZT were mediated by genes associated with hormone and steroid metabolism, as well as pathways involved in steroid hormone biosynthesis and cytochrome P450 enzymes. Docking results showed free-binding energies ranging from -6.06 to -10.85 kcal/mol, indicating strong binding affinity between the compounds and targets. Molecular dynamics simulation results further confirmed the stability of these interactions. Conclusion: This study demonstrates that YHZT treats PD by suppressing inflammatory reactions and modulating hormone and cytochrome P450 concentrations. Key compounds such as ferulic acid, (R)-canadine, (S)-canadine, canadine, and asristolone are implicated in this process. These findings offer insights into the mechanisms underlying the action of YHZT and provide a foundation for further research in this area.

Mechanistic exploration and experimental validation of the Xiaochaihu decoction for the treatment of breast cancer by network pharmacology.

Xiaochaihu (XCH) decoction is a traditional Chinese prescription that has been recorded in the pharmacopeia of the People's Republic of China. In China, the XCH decoction is used clinically to treat a variety of tumors, including breast cancer. However, its potential mechanism of action is still undefined. The chemical compounds in the XCH decoction were identified via Q Exactive Orbitrap LC-MS/MS. Then, we screened the active ingredients and targets in the XCH decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Next, Cytoscape and Metascape were used to construct an active ingredient-target-disease network, which included a protein-protein interaction (PPI) network, GO enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, we used molecular docking and in vitro experiments to verify the results of network pharmacology analysis. More than 70 major compounds were identified by Q Exactive Orbitrap LC-MS/MS analysis from the XCH decoction. A total of 162 active ingredients and 153 targets related to the XCH decoction and breast cancer were identified, and a compound-target-disease network was constructed. GO and KEGG analyses revealed that the XCH decoction regulated the drug response, apoptosis process, cancer pathway, and PI3K/Akt signaling pathway. Molecular docking and experimental validation indicated that the XCH decoction suppressed proliferation and induced apoptosis in breast cancer cells by regulating the expression of apoptosis-related proteins and inhibiting the PI3K/Akt pathway. This study suggested that the XCH decoction can be used to treat breast cancer by inhibiting cell proliferation, inducing apoptosis and downregulating the PI3K/Akt signaling pathway.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

Yantiao Formula intervention in Rats with Sepsis: Network Pharmacology and Experimental Analysis.

Traditional Chinese Medicine prescribes Yantiao Formula (YTF; peach kernel, mirabilite, Angelica sinensis, Radix Scrophulariae, raw rhubarb, Radix Paeoniae, Flos Lonicerae, Forsythia, and Ophiopogon japonicus) to treat sepsis. Clinically, it reduced the inflammatory response of sepsis. It also reduced lung damage by decreasing the level of TNF-α in septic rats' serum. Using network pharmacology analysis, we investigated the efficacy network and mechanism of YTF in treating sepsis. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine (BATMAN-TCM) combined with literature to collect the main components in YTF and their targets. DisGeNET and GENECARDS databases were used for sepsis-related targets. Cytoscape 3.7.1 software was used to construct the herbcomponent- target and ingredient-target-disease interaction protein-protein interaction networks of YTF. The jvenn was used to perform the intersection of YTF targets and sepsis targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed． We also created a sepsis rat model using cecal ligation and perforation and stimulated alveolar macrophages (NR8383) with endotoxin to investigate the mechanisms of YTF. GO, and KEGG enrichment analysis revealed that these targets involved mineralocorticoid secretion, aldosterone secretion, active regulation of chronic inflammatory response, the exogenous coagulation pathway, and other pathophysiology. It was linked to various inflammatory factors and the MAPK pathway. YTF inhibits the p38MAPK pathway and decreases TNF- α, IL-6, and CXCL8 levels. YTF has a multi-component, multi-target, and multi-channel role in treating sepsis. The primary mechanisms may involve inhibiting the p38MAPK pathway to reduce the inflammatory response.

Analysis of the Mechanism of Intervention of Fangxiangxiaozhi Prescription on Dyslipidemia Based on Network Pharmacology and Molecular Docking

Objective: To explore the mechanism of intervention of Fangxiangxiaozhi prescription on dyslipidemia by using network pharmacology and molecular docking. Methods: The traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pubchem, Uniprot, and other databases were adopted to screen the active ingredients and the corresponding targets of Fangxiangxiaozhi prescription. Dyslipidemia-related targets were identified using the databases of Disgenet and GeneCards. Then, the intersection target of drugs and diseases was demonstrated via a Venn diagram. Cytoscape3.7.2 was used to construct a “drugs-active ingredients-intersection targets” network map and the key active ingredients with the top 7-degree values were determined. The protein interaction network and topology analysis of the intersection target genes were carried out by combining STRING11.0 and Cytoscape3.7.2. Moreover, the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the intersection target genes were carried out using the Metascape database. Lastly, the key active ingredients and targets were molecular docked by AutoDockTools, Pymol, and other software. Results: There were 51 active components and 509 target genes of which 74 intersect with dyslipidemia. The key targets included tumor necrosis factor (TNF), interleukin-6 (IL-6), AKT1, PPAR gamma (PPARG), VEGFA, and PPARα. GO enrichment analysis obtained 1040 biological processes, 33 cell components, and 84 molecular functions; KEGG enrichment analysis obtained 148 pathways. The molecular docking results showed that the key targets and compounds exhibited good binding force. Conclusion: The active ingredients of Fangxiangxiaozhi prescription regulated several pathways through multiple targets to intervene in dyslipidemia. This study can serve as a foundation for further research.

Investigating the Mechanism of Banxia Xiexin Decoction in Treating Gastritis and Diabetes Mellitus through Network Pharmacology and Molecular Docking Analysis

Background: Banxia Xiexin decoration (BXD), a complex prescription in Traditional Chinese Medicine (TCM), clinically acts as a treatment for gastritis and diabetes while its mechanism of treatment remains unknown. Objection: This study aimed to explore the common mechanism of BXD in treating gastritis and diabetes based on network pharmacology and molecular docking technology. Methods: The seven Chinese herbal components and drug targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) for gastritis and diabetes using GeneCards, DisGeNET, Comparative Toxicogenomics Database (CTD), and Online Mendelian Inheritance in Man (OMIM) databases. Common drug and disease targets were imported into the STRING data platform for protein-protein interaction (PPI) analysis, and Cytoscape 3.7.2 software for network topology analysis, and core targets were filtered. Results: There were 124 components, 249 targets, 449 targets for gastritis, and 4005 targets for diabetes. After mapping, 83 BXD targets for gastritis and diabetes were obtained, and the targets with high correlation were STAT 3, JUN, TNF, IL-6, etc. More relevant targets were involved in the cancer pathway, AGE-RAGE signaling pathway of diabetic complications, fluid shear stress, and atherosclerosis pathway. Conclusion: This study preliminarily reveals that BXD may play a role in the treatment of gastritis and diabetes mellitus through multi-components, multi-targets, and multi-pathways, and proposes some potential "component-target-pathway" hypotheses in light of previous reports.

Multitarget Mechanism of Artemisia Plants to Fight Respiratory Tract Infections Based on Network Pharmacology and Molecular Docking

Objective: To study the mechanism of Artemisia in the treatment of respiratory tract infection (RTI) by network pharmacology and molecular docking. Methods: The active constituents and targets of Artemisia were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database to obtain disease targets associated with RTI. The key targets of intersection were used to construct the protein–protein interaction (PPI) network, and the hub gene was obtained through topological analysis to construct the pharmacology regulation network of traditional Chinese medicine. The key targets were analyzed by R language enrichment, and the regulatory network diagram of the key target function/pathway was constructed. Molecular docking verifies the binding of the drug to the target predicted by network pharmacology. Results: 144 active components of Artemisia regulated 133 target proteins related to RTI, the core components were β-sitosterol, quercetin, isorhamnetin, artemisinin, etc. Gene ontology enrichment analysis showed that Artemisia regulates receptor ligand activity, cytokine activity, and other molecular functions by acting on membrane region, membrane raft and other cellular structures in the treatment of RTI, thus affecting biological processes such as the response to drugs and bacteria-derived molecules. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), tumor necrosis factor, interleukin-17 (IL-17) signaling pathway was the main pathway for RTI treatment. The molecular docking method confirmed the high affinity between the active ingredient and the RTI target. Conclusions: Artemisia species, a multitarget medication, has been shown to be a viable therapy option for RTI by network pharmacology techniques based on data mining and molecular docking approaches.

Mechanism of Danggui Buxue decoction in the treatment of myocardial infarction based on network pharmacology and experimental identification

BackgroundMyocardial infarction (MI) remains one of the major causes of high morbidity and mortality worldwide. Danggui Buxue Decoction (DBD)—an ancient Chinese herbal decoction—has been used to prevent coronary heart disease, which was called “chest palsy” in ancient clinics. However, the mechanism of DBD in the treatment of MI remains unclear. The aim of this study was to explore the effect and mechanism of DBD on MI by combining network pharmacology with in vivo experiments. Materials and methodsFirst, public databases were used to identify the key active chemicals and possible targets of DBD. The MI targets were obtained from the Therapeutic Target Database, and the function of the target genes in relation to linked pathways was investigated. Subsequently, Cytoscape software was used to build a target-signaling pathway network. Finally, the efficacy of DBD therapy on MI was validated using in vivo investigations combined with molecular docking. ResultsIn traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), 27 bioactive compounds were screened from DBD. A total of 213 common targets were obtained, including 507 DBD targets and 2566 MI targets. Enrichment analysis suggests that PI3K/AKT is a potential signaling pathway for DBD-based protection. Immunofluorescence and protein blotting confirmed PI3K/AKT1, ERK2, and CASPASE-9 as the target proteins. Molecular docking analysis showed that quercetin, kaempferol, isoflavanones, isorhamnetin, hederagenin, and formononetin had high binding affinity to AKT1, ERK2, and CASPASE-9. ConclusionsThis study demonstrated that the therapeutic benefit of DBD on MI may be mediated via target proteins in the PI3K/AKT pathway, such as AKT1, ERK2, and CASPASE-9. Our study data can help to provide ideas and identify new treatment targets for MI.

Mechanism of pruritus ani lotion combined with Huajiao-Gancao-Bingpian oil for pruritus ani treatment based on network pharmacology and molecular dynamics.

Pruritus ani lotion combined with a Chinese medicine formula named Huajiao (Pericarpium Zanthoxyli Bungeani)-Gancao (Radix Glycyrrhizae)-Bingpian (Borneol) is effective in treating pruritus ani. To investigate the mechanism of traditional Chinese medicine (TCM) in pruritus ani via network pharmacology and molecular dynamics (MD). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilised to screen active ingredients and their corresponding targets. Genes associated with pruritus ani were collected through GeneCards. Protein-protein interaction (PPI) network between target genes of the active ingredients of this formula and genes associated with pruritus ani was established through the STRING database. A drug-active ingredient-gene interaction network was constructed using Cytoscape with the top 50 genes in affinity coefficients. Molecular docking and MD simulation analysis were performed. Epidermal growth factor receptor (EGFR) and Signal Transducer and Activator of Transcription 3 (STAT3) were core genes. Direct targeting of EGFR by the active ingredients (quercetin and luteolin) and direct targeting of STAT3 by the active ingredient (licochalcone A) may be key molecular mechanisms for the treatment of pruritus ani. Simulated trajectories of structural nuclear motion by MD also revealed that the binding of two pairs of molecules was relatively stable. This study unravels potential targets, active ingredients, and mechanisms of pruritus ani lotion combined with Huajiao-Gancao-Bingpian oil in the treatment of pruritus ani, providing a reference for future treatment.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction against renal fibrosis.

To investigate the mechanism by which Sini decoction (, SND) improves renal fibrosis (Rf) in rats based on transforming growth factor β1/Smad (TGF-β1/Smad) signaling pathway. Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf. The targets of SND drug components and the targets of Rf were obtained by searching databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP) and GeenCard. The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram. Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway. The Rf rat model was established by unilateral ureteral occlusion (UUO). The expression levels of transforming growth factor, matrix metalloproteinase-9 (MMP-9), matrix metal protease-2 (MMP-2), connective tissue growth factor (CTGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by Masson staining of rat renal tissue, and immunohistochemical methods. The expression levels of Smad3, Smad2, and Smad7 in renal tissue were determined by Western blotting (WB). The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway. A total of 12 drug components of Fuzi (Radix Aconiti Lateralis Preparata), 5 drug components of Ganjiang (Rhizoma Zingiber), and 9 drug components of Gancao (Radix Glycy et Rhizoma) were obtained from the database search, and 207 shared targets were found. A total of 1063 Rf targets were found in the database search. According to the Venn diagram, in total, 96 intersection targets were found in two database searches. The metabolic pathways involved included TGF-β signaling pathway, phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling (PI3K/Akt) pathway, and hypoxia-inducible factor-1 (HIF-1) signaling pathway. Masson staining analysis showed that compared with the model group, the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower (P < 0.05). Immunohistochemical analysis, compared with the control group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased (P < 0.01). Compared with the model group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased (P < 0.05, P < 0.01). WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3 (P < 0.05) and increase the expression of Smad7 (P < 0.05).

Identification of Dalbergiae Odoriferae Lignum active ingredients and potential mechanisms in the treatment of adriamycin-induced cardiotoxicity based on network pharmacology and experimental verification.

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.

Exploration of Ginkgo biloba leaves on non-small cell lung cancer based on network pharmacology and molecular docking.

Pharmacological studies have found Ginkgo biloba leaves have the effect of inhibiting neoplasms, it is clinically used in treating various neoplasms. However, the mechanism of Ginkgo biloba leaves in treating non-small cell lung cancer (NSCLC) remains unclear. The active components and corresponding targets of Ginkgo biloba leaves were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the targets of NSCLC were obtained from the GeneCards, OMIM, TTD, and DrugBank databases. The common targets of NSCLC and Ginkgo biloba leaves were obtained from VENNY 2.1.0. The STRING database was utilized to construct protein-protein intersections, by using the Cytoscape 3.7.1 software, the protein-protein intersection was optimized and the drug-disease network diagram was constructed. The DAVID database was utilized to perform GO and KEGG analysis. Finally, The Autodock Vina software was used to perform molecular docking of core components and targets. The key components of Ginkgo biloba leaves in treating NSCLC include quercetin, luteolin, and kaempferol, which may act on Tp53, AKT1, and TNF. Bioinformatic annotation analysis results suggest that Ginkgo biloba leaves may implicated in PI3K-AKT and MAPK signaling pathways. The molecular docking results show the firm affinity between key ingredients and targets. The potential mechanism of Ginkgo biloba leaves in treating NSCLC has been discussed in this study, which provides a theoretical basis for the clinical treatment of NSCLC and further experimental validation.

Research on the Mechanism of Si Xian Decoction in Treating Acute Leukemia Based on Network Pharmacology and Molecular Docking Technology

Abstract Objective Our objective was to investigate the mechanism of action of the Si Xian Decoction (SXD) in treating acute leukemia (AL) using network pharmacology and molecular docking techniques. Methods The chemical components of the four medicinal herbs of Shengdi (Rehmanniae Radix), Baimaogen (Imperatae Rhizoma), Xiaoji (Cirsii Herba), and Pugongying (Taraxaci Herba) in the SXD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), and Encyclopedia of Traditional Chinese Medicine (ETCM). A natural active chemical component dataset for the SXD was established. Human Gene Database (Gencards), Database of Gene-Disease Associations (DisGeNET), Database for Drug and Drug Target Information (DrugBank), and Human Disease Database (MalaCards) were searched to obtain AL-related targets and to establish a disease target database. After obtaining the intersection targets of drugs and diseases, a Venn diagram of the common targets was drawn online. A drug-disease protein interaction network was constructed using the String 11.5 platform, and a “drug-disease-target-signal pathway” network was built using Cytoscape 3.8.2 software to obtain relevant target network topology parameters. Results By searching the TCMSP, BATMAN-TCM, and ETCM databases, 30 active components of the SXD and 677 related targets were obtained. From Gencards, DrugBank, MalaCards, and DisGeNET databases, 12,110 potential AL disease targets were obtained. Using the ClusterProfiler package of the R4.2.2 platform, 1,011 entries of gene ontology information were enriched, including 467 biological process entries, 236 molecular function entries, and 308 cellular component entries. Additionally, 220 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were obtained, mainly involving chemical carcinogen receptor activation, lipid and atherosclerosis, fluid shear stress and atherosclerosis, prostate cancer, and the role of the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications. Network topology analysis revealed that the main active components of SXD treating AL include γ-aminobutyric acid, adenosine, quercetin, scopolamine, and taraxasterol. Conclusion The treatment of AL with the SXD is a process of multicomponent, multitarget, and multisignal pathway coordination. Network pharmacology provides a solid research basis for elucidating the mechanism of action of SXD in the treatment of AL.

The Mechanism of Plantaginis Semen in the Treatment of Diabetic Nephropathy based on Network Pharmacology and Molecular Docking Technology.

Diabetic nephropathy (DN) is one of the common complications of diabetes. Plantaginis Semen (PS) has a variety of therapeutic effects, however its mechanism on DN is unclear. This paper aims to find the ingredients, the key targets, and the action pathways of PS on DN from the perspective of network pharmacology. The databases of network pharmacology, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pharmmapper, OMIM, DrugBank, Gene- Cards, TTD, Disgenet, STRING, and Cytoscape software, were used to find the main ingredients and targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genome and Genomes (KEGG) pathway enrichment analysis were used to reveal the potential pathways of the PS on DN. The GEO database was used to find the targets of DN based on valid experimental research. The molecular docking technology was used to evaluate the combination between ingredients of PS and the targets. A total of 9 active ingredients and 216 potential therapeutic targets were obtained for PS on DN. Hub targets were discovered by the Cytoscape software analysis. CASP3 was screened by Venn diagram by making intersection between GSE30529 and hub genes. Moreover, CASP3 was combined with one of the nine active ingredients, quercetin, by molecular docking analysis. The KEGG pathways were mainly involved in diabetic nephropathy, and were simultaneously associated with CASP3 as followed: AGE-RAGE signaling pathway in diabetic complications, apoptosis, lipid and atherosclerosis, MAPK signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and p53 signaling pathway. PS can have the treatment on DN through CASP3. Quercetin, as one of the nine active ingredients, can be bounded to CASP3 to inhibit apoptosis in DN. PS can also take action on DN probably through many pathways. The role of PS on DN through other pathways still needs to be further elaborated.

Biomarkers and coptis chinensis activity for rituximab-resistant diffuse large B-cell lymphoma: Combination of bioinformatics analysis, network pharmacology and molecular docking.

Rituximab resistance is one of the great challenges in the treatment of diffuse large B-cell lymphoma (DLBCL), but relevant biomarkers and signalling pathways remain to be identified. Coptis chinensis and its active ingredients have antitumour effects; thus, the potential bioactive compounds and mechanisms through which Coptis chinensis acts against rituximab-resistant DLBCL are worth exploring. To elucidate the core genes involved in rituximab-resistant DLBCL and the potential therapeutic targets of candidate monomers of Coptis chinensis. Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Similarity Ensemble Approach and Swiss Target Prediction, the main ingredients and pharmacological targets of Coptis chinensis were identified through database searches. Through the overlap between the pharmacological targets of Coptis chinensis and the core targets of rituximab-resistant DLBCL, we identified the targets of Coptis chinensis against rituximab-resistant DLBCL and constructed an active compound-target interaction network. The targets and their corresponding active ingredients of Coptis chinensis against rituximab-resistant DLBCL were molecularly docked. Berberine, quercetin, epiberberine and palmatine, the active components of Coptis chinensis, have great potential for improving rituximab-resistant DLBCL via PIK3CG. This study revealed biomarkers and Coptis chinensis-associated molecular functions for rituximab-resistant DLBCL.

Validating core therapeutic targets for osteoporosis treatment based on integrating network pharmacology and informatics

ObjectiveOur goal was to find metabolism-related lncRNAs that were associated with osteoporosis (OP) and construct a model for predicting OP progression using these lncRNAs. MethodsThe GEO database was employed to obtain gene expression profiles. The WGCNA technique and differential expression analysis were used to identify hypoxia-related lncRNAs. A Lasso regression model was applied to select 25 hypoxia-related genes, from which a classification model was created. Its robust classification performance was confirmed with an area under the ROC curve close to 1, as verified on the validation set. Concurrently, we constructed a ceRNA network based on these genes to unveil potential regulatory processes. Biologically active compounds of STZYD were identified using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database. BATMAN was used to identify its targets, and we obtained OP-related genes from Malacards and DisGeNET, followed by identifying intersection genes with metabolism-related genes. A pharmacological network was then constructed based on the intersecting genes. The pharmacological network was further integrated with the ceRNA network, resulting in the creation of a comprehensive network that encompasses herb-active components, pathways, lncRNAs, miRNAs, and targets. Expression levels of hypoxia-related lncRNAs in mononuclear cells isolated from peripheral blood of OP and normal patients were subsequently validated using quantitative real-time PCR (qRT-PCR). Protein levels of RUNX2 were determined through a western blot assay. ResultsCBFB, GLO1, NFKB2 and PIK3CA were identified as central therapeutic targets, and ADD3-AS1, DTX2P1-UPK3BP1-PMS2P11, TTTY1B, ZNNT1 and LINC00623 were identified as core lncRNAs. ConclusionsOur work uncovers a possible therapeutic mechanism for STZYD, providing a potential therapeutic target for OP. In addition, a prediction model of metabolism-related lncRNAs of OP progression was constructed to provide a reference for the diagnosis of OP patients.

Mechanism of Guizhi Gancao Decoction against myocardial ischemia-reperfusion injury based on network pharmacology and experimental verification

This study employed network pharmacology to investigate the effect of Guizhi Gancao Decoction(GGD) on myocardial ischemia-reperfusion injury(MI/RI) in rats and decipher the underlying mechanism. Firstly, the chemical components and targets of GGD against MI/RI were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), SwissTargetPrediction, and available articles. STRING and Cytoscape 3.7.2 were used to establish the protein-protein interaction(PPI) network for the common targets, and then Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out for the core targets. The &quot;drug-active component-target-pathway&quot; network was built. Furthermore, molecular docking between key active components and targets was conducted in AutoDock Vina. Finally, the rat model of MI/RI was established, and the myocardial infarction area was measured. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to detect cardiomyocyte pathology and ultrastructural changes. Western blot was employed to determine the expression of related proteins in the myocardial tissue. A total of 75 chemical components of GGD were screened out, corresponding to 318 targets. The PPI network revealed 46 core targets such as tumor protein p53(TP53), serine/threonine kinase 1(AKT1), signal transducer and activator of transcription 3(STAT3), non-receptor tyrosine kinase(SRC), mitogen-activated protein kinase 1(MAPK1), MAPK3, and tumor necrosis factor(TNF). According to GO and KEGG enrichment analyses, the core targets mainly affected the cell proliferation and migration, signal transduction, apoptosis, and transcription, involving advanced glycation end products-receptor(AGE-RAGE), MAPK and other signaling pathways in cancers and diabetes complications. The molecular docking results showed that the core components of GGD, such as licochalcone A,(+)-catechin, and cinnamaldehyde, had strong binding activities with the core target proteins, such as MAPK1 and MAPK3. The results of animal experiments showed that compared with the model group, GGD significantly increase superoxide dismutase, decreased malondialdehyde, lactate dehydrogenase, and creatine kinase-MB, and reduced the area of myocardial infarction. HE staining and TEM results showed that GGD pretreatment restored the structure of cardiomyocytes and alleviated the pathological changes and ultrastructural damage of mitochondria in the model group. In addition, GGD significantly down-regulated the phosphorylation of c-Jun N-terminal kinase and p38 and up-regulate that of extracellular regulated kinases 1/2 in the myocardial tissue. The results suggested that GGD may exert the anti-MI/RI effect by regulating the MAPK signaling pathway via the synergistic effects of Cinnamomi Ramulus and Glycyrrhizae Radix et Rhizoma.

A Strategy based on Bioinformatics and Machine Learning Algorithms Reveals Potential Mechanisms of Shelian Capsule against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and life-threatening form of cancer, with Shelian Capsule (SLC), a traditional Chinese medicine (TCM) formulation, being recommended for clinical treatment. However, the mechanisms underlying its efficacy remain elusive. This study sought to uncover the potential mechanisms of SLC in HCC treatment using bioinformatics methods. Bioactive components of SLC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and HCC-related microarray chip data were sourced from the Gene Expression Omnibus (GEO) database. The selection criteria for components included OB ≧ 30% and DL ≧ 0.18. By integrating the results of differential expression analysis and weighted gene co-expression network analysis (WGCNA), disease-related genes were identified. Therapeutic targets were determined as shared items between candidate targets and disease genes. Protein-protein interaction (PPI) network analysis was conducted for concatenated genes, with core protein clusters identified using the MCODE plugin. Machine learning algorithms were applied to identify signature genes within therapeutic targets. Subsequently, immune cell infiltration analysis, single-cell RNA sequencing (sc-RNA seq) analysis, molecular docking, and ADME analysis were performed for the screened genes. A total of 153 SLC ingredients and 170 candidate targets were identified, along with 494 HCCrelated disease genes. Overlapping items between disease genes and drug candidates represented therapeutic genes, and PPI network analysis was conducted using concatenated genes. MCODE1 and MCODE2 cluster genes underwent Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Four signature genes (TOP2A, CYP1A2, CYP2B6, and IGFBP3) were identified from 28 therapeutic genes using 3 machine learning algorithms, with ROC curves plotted. Molecular docking validated the interaction modes and binding abilities between signature genes and corresponding compounds, with free binding energy all <-7 kcal/mol. Finally, ADME analysis revealed similarities between certain SLC components and the clinical drugs Sorafenib and Lenvatinib. In summary, our study revealed that the mechanism underlying the anti-HCC effects of SLC involves interactions at three levels: components (quercetin, beta-sitosterol, kaempferol, baicalein, stigmasterol, and luteolin), pathways (PI3K-Akt signaling pathway, TNF signaling pathway, and IL-17 signaling pathway), and targets (TOP2A, CYP1A2, CYP2B6, and IGFBP3). This study provides preliminary insights into the potential pharmacological mechanisms of SLC in HCC treatment, aiming to support its clinical application and serve as a reference for future laboratory investigations.

Systematic Pharmacology and Experimental Validation to Reveal the Alleviation of Astragalus membranaceus Regulating Ferroptosis in Osteoarthritis.

Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear. We validated AM's protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM's active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments. AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM's ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis. This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM's scientific application.