Background Although Rhizoma Chuanxiong has been used for the treatment of diabetic kidney disease (DKD), the relevant mechanisms remain unclear. The purpose of this study was to investigate the potential targets and mechanisms of Rhizoma Chuanxiong in treating DKD, utilizing network pharmacology. Methods Active compounds of Rhizoma Chuanxiong were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform database. SwissTargetPrediction was used to obtain the potential targets of active ingredients. DKD-associated targets were gathered from the GeneCards, DisGeNET, and OMIM databases. The STRING database and Cytoscape 3.7.2 were used for investigating core targets and interactions among targets. Gene Ontology and Kyoto Encyclopedia of Gene Genomes enrichment were performed using DAVID database. Molecular docking was performed using AutoDock-1.5.7 based on the crystal structures of the targets as deposited in the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank. Results The top 10 core targets were identified, namely PPARG, AKT1, EGFR, STAT3, CASP3, PPARA, ICAM1, PTGS2, SRC, and MMP9. Enrichment analysis revealed that the primary pathways involving these targets including prolactin signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, VEGF signaling pathway, and FoxO signaling pathway. Molecular docking demonstrated that mandenol exhibited a strong binding affinity toward EGFR domain, and wallichilide displayed pronounced binding affinity toward AKT1, EGFR, STAT3, and PTGS2 domains. Additionally, myricanone and senkyunone also showed strong binding affinity for AKT1, EGFR, CASP3, STAT3, and PTGS2 domains. Conclusions This study revealed the potential multi-component and multi-target mechanisms of Rhizoma Chuanxiong in treating DKD through network pharmacology. Supplementary experiments are required to further verify these findings.

Background:Semen strychni is commonly used to treat gliomas in China. However, the underlying mechanism of action of semen strychni in glioma treatment remains unknown. Using network pharmacology and molecular docking, we investigated the probable pharmacological mechanisms of semen strychni in glioma treatment.Methods:The active components of semen strychni were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Using the Cytoscape program created the active component-target network diagram of semen strychni. The GeneCards, DisGeNET, and Online Mendelian Inheritance in Man databases were used to compile the list of targets related to glioma. Using the STRING database created a protein–protein interaction network of popular drugs and disease targets. For Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis of common targets, the Database for Annotation, Visualization and Integrated Discovery database was utilized. In order to identify the main targets of semen strychni in the treatment of glioma, a target-pathway interaction network was built. The molecular docking of critical and crucial components was done using AutoDock. Glioma samples from the Cancer Genome Atlas and Human Protein Atls databases were extracted to detect the mRNA and protein expression levels of ADRB1 and ADRB2 and analyze the correlation between expression and survival of glioma patients. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, Transwell, and wound healing assays validate the effect of stigmasterol on the malignant progression of glioma cells.Results:The core components of semen strychni used in the treatment of glioma included stigmasterol, (S)-stylopine, isobrucine, icaride A, and isostrychnine N-oxide (I), which may operate on core targets such as ADRB1, ADRB2, CHRM3, ADRA1A, and ESR1. The significant pathways discovered using Kyoto Encyclopedia of Genes and Genomes enrichment analysis were chemical carcinogenesis-receptor activation, calcium signaling pathway, and pathways in cancer. The outcomes of the molecular docking demonstrated a strong affinity between the central targets and elements. Data from the Cancer Genome Atlas and Human Protein Atls databases indicate that ADRB1 and ADRB2 are expressed in glioma, and high expression of ADRB2 may predict a good outcome. In vitro experimental results indicate that stigmasterol can inhibit the malignant progression of U251 cells.Conclusion:This article discusses the probable mechanism of action of semen strychni in the treatment of glioma, which can serve as a theoretical basis and evidence for subsequent experimental investigations.

ABSTRACTIntroductionHerbal formulations have been used for skin whitening in China for centuries, yet systematic evaluations of their efficacy and underlying mechanisms remain limited. This study aims to identify potential anti‐melanogenic compounds in traditional skin‐whitening herbs using network pharmacology and investigate their mechanisms of action.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen for anti‐melanogenic compounds and their potential targets. A protein–protein interaction (PPI) network was constructed using Cytoscape 3.7.2, followed by KEGG pathway enrichment analysis. The pharmacological effects were assessed in a 3D human skin model, and in vitro experiments were conducted to explore the molecular mechanisms of the identified compounds.ResultsEight potential skin‐whitening herbs were identified, including Ampelopsis japonica, Nepeta tenuifolia Benth., Scutellaria baicalensis Georgi, Asarum heterotropoides F. Schmidt, Ipomoea nil, Angelica dahurica, Angelica sinensis, and Prunus persica, along with ten active compounds: quercetin, kaempferol, wogonin, beta‐sitosterol, baicalein, stigmasterol, anhydroicaritin, agroclavin, moslosooflavone, and acacetin. Among them, quercetin and acacetin demonstrated significant anti‐melanogenic effects in the 3D skin model by downregulating ET‐1, VEGF, and PTGS2 in keratinocytes. Molecular docking analysis further revealed strong binding affinities of quercetin and acacetin to TLR4, CHUK, and RELA in the NF‐κB pathway, suggesting their role in melanogenesis inhibition via suppression of keratinocyte paracrine signaling.ConclusionsThis study highlights the potential of network pharmacology as an effective approach for screening anti‐melanogenic compounds from traditional skin‐whitening herbs. Quercetin and acacetin were identified as key bioactive compounds that inhibit melanogenesis by modulating keratinocyte signaling pathways.

Radiation therapy is a crucial method used to treat various tumors, but it can lead to radiation pneumonitis. Shashen Maidong Decoction (SMD) is clinically used to treat radiation pneumonitis, but the exact mechanism remains unclear. Herbal components and targets of SMD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Encyclopedia of Traditional Chinese Medicine (ETCM), and Swiss Target Prediction platforms. Moreover, disease-related targets were retrieved from the GeneCards database. A Protein-protein Interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database. Subsequently, the disease-active component-target network and drug-pathway-target network were constructed using Cytoscape. The molecular docking results were validated and visualized using Auto Dock and PyMOL software. In this study, 115 conserved active ingredients, 316 drug targets, and 355 radiation pneumonitis targets were identified. Among these, 75 targets were identified as intersecting targets. GO enrichment analysis revealed 494 biological processes, 36 cell components, and 59 molecular functions. KEGG analysis uncovered 118 signaling pathways, including the IL17 signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, etc. The molecular docking results showed the core active ingredients of SMD, including quercetin, kaempferol, beta-carotene, and naringenin, to have strong binding ability with the core targets. This study preliminarily confirmed that SMD may act on the TNF, IL17, and HIF-1 signaling pathways to exert its therapeutic effects on radiation pneumonitis by regulating the expression of inflammatory factors.

Lipopolysaccharide (LPS) can trigger an inflammatory response in lung epithelial cells, which may contribute to the development of Acute Respiratory Distress Syndrome (ARDS). Epigallocatechin-3- gallate (EGCG), a bioactive constituent in green tea, is widely acknowledged for its anti-inflammatory characteristics. This study explored the anti-inflammatory effects of EGCG and its potential molecular mechanisms in mouse lung epithelial-12 (MLE-12) cells. MLE-12 cells were pre-exposed to increasing EGCG concentrations (5, 7.5, and 10 µM) for 24 h, followed by exposure to LPS (20 ng/mL) to induce inflammation After induction, cell and supernatant samples were collected. A range of detection methods were applied to systematically assess the anti-inflammatory activities and the latent mechanisms of EGCG, comprising real-time polymerase chain reaction assay (RT-PCR), enzyme-linked immunosorbent assays (ELISA), western blotting, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), transcriptome sequencing, immunofluorescence, co-immunoprecipitation, and confocal microscopy imaging. EGCG exhibited anti-inflammatory effects in LPS-stimulated MLE-12 cells by inhibiting the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Its primary mechanism involves robust attachment to 67-kDa laminin receptor (67LR), which modulates the interaction between 67LR and the JAK2 protein within the JAK2/STAT3 signaling pathway. This results in a considerable diminishment in LPS-induced production and expression of inflammatory-promoting cytokines in MLE-12 cells. EGCG attenuates the inflammatory reaction in MLE-12 cells by binding to 67LR and inhibiting the JAK2/STAT3 signaling pathway. The current study explored the effects of EGCG on LPS-induced inflammation in MLE-12 cells, which may offer some new perspectives in inflammation research and broadening our comprehension of the fundamental mechanisms inflammation-related diseases. Considering EGCG’s role in suppressing inflammation in MLE-12 cells, it is reasonable to advocate, from a preventive perspective, the inclusion of EGCG-rich foods as a dietary component for helping alleviate the probability of inflammation-associated disorders.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26875-4.

Venous thrombosis presents a significant global health challenge, characterized by its high incidence and limited therapeutic effectiveness. Our objective is to leverage the pharmacological insights offered by traditional Chinese medicine networks to identify potential therapeutic targets for venous thrombosis treatment and elucidate their underlying mechanisms of action. We initiated our study by isolating the active ingredients and targets of Chinese medicine compounds from the traditional Chinese medicine systems pharmacology database. Concurrently, we acquired venous thromboembolism (VTE) patient data from the gene expression omnibus dataset. Utilizing cytoscape, we constructed a network connecting traditional Chinese medicine ingredients, disease targets, and related interactions. Molecular subtypes were determined through target information clustering and typing using the “ConsensusClusterPlus” software package. Key genes were subsequently identified through a combination of weighted gene co-expression network analysis and machine learning techniques. Functional enrichment analysis was performed on these key genes. Subsequently, we investigated immune cell and immune function differences related to the identified key genes. Lastly, we constructed the competing endogenous RNA network associated with PPP2R1A. Our initial analysis identified several key genes, including FOS, ICAM1, CASP3, and HSP90AA1. Subsequent functional and downstream analyses revealed that 2 central hub genes, PPP2R1A and ribosomal protein L9, may represent novel targets for VTE therapy. Notably, these hub genes are not only associated with thrombospondin and platelet function regulation but also play a role in modulating T cell expression in immunoassays. In conclusion, our findings suggest that 10 long non-coding RNAs may compete with 2 microRNAs for binding, thereby regulating PPP2R1A target genes, with potential implications for improving VTE treatment efficacy. Our current findings offer a novel direction and serve as a theoretical foundation for identifying therapeutic targets in the treatment of VTE. Furthermore, these findings hold the potential to facilitate the translation of our research into clinical applications in the future.

Based on the gene expression omnibus database, the immune-related genes associated with refractory lupus nephritis (RLN) are analyzed by comparing the RNA expression data of drug-sensitive lupus nephritis (DLN) with that of RLN. Subsequently, potential therapeutic drugs were screened based on the identified genes. The RNA expression datasets related to DLN and RLN were sourced from the gene expression omnibus database. Differential analysis was performed to ascertain differentially expressed genes. These differentially expressed genes were then cross-referenced with immune-related genes obtained from the ImmPort database to identify potential candidate genes. To investigate the underlying biological mechanisms, gene ontology and kyoto encyclopedia of genes and genomes analyses were performed. Core genes were subsequently identified using the STRING database, along with least absolute shrinkage and selection operator regression analysis and support vector machine-recursive feature elimination (SVM-RFE) techniques. The receiver operating characteristic curve was utilized to confirm and assess the significance of the core genes. A nomogram prediction model was developed, with the concordance index (C-index) applied to evaluate its precision. The immune cell infiltration in both RLN and DLN was examined, investigating the relationships between core genes and immune cells, as well as interactions among the immune cells. Coremine Medical was engaged to discover traditional Chinese medicines that exhibited significant associations with the core genes. Additionally, the Traditional Chinese Medicine Systems Pharmacology database was employed to identify small molecule compounds with therapeutic potential found within these traditional medicines. Finally, the protein structures of the key genes and their corresponding small molecule compounds were processed using Vina software and PyMol software for molecular docking, ensuring the reliability of the results. In this investigation, a total of 5 essential genes were pinpointed: MMP-9, IRF7, CCR6, OAS1, and IFIH1. Furthermore, small molecule compounds that may have therapeutic potential were identified based on these central genes, including tanshinone IIA (Tan IIA), luteolin, ellagic acid, baicalein, and quercetin. The immune mechanism of RLN is complex, arising from a synergy of multiple factors, targets, and pathways. This approach is valuable for elucidating the mechanisms underlying RLN resistance and offers a novel perspective for enhancing immunotherapy effectively.

Premature ovarian insufficiency (POI) is a condition marked by diminished ovarian function and reduced fertility, caused by the chemotherapy drug cyclophosphamide (CTX) used to treat gynecologic cancers. The abnormal inflammation of ovarian tissue induced by CTX represents a key factor that impairs follicular cells and disrupts fertility. Therefore, the present study aims to investigate the underlying mechanisms of CTX-induced abnormal ovarian inflammation and identify potential therapeutic agents. RNA sequencing data derived from CTX-induced mouse ovarian tissues were first intersected with inflammation-related genes retrieved from the Gene Ontology (GO) database. This was followed by functional enrichments analysis and protein-protein interaction (PPI) analyses to identify target genes. Subsequently, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was screened to obtain corresponding candidate therapeutic agents. Finally, a CTX-induced mouse model was established to verify the therapeutic efficacy of the candidate drug and elucidates its underlying mechanisms. A total of 25 candidate genes were identified, with interleukin 1β (IL1β) confirmed as the core gene. Subsequent screening resulted in the identification of Irisolidone as a potential therapeutic agent. The present study demonstrated that Irisolidone ameliorates CTX-induced follicular cell developmental impairment and improves fertility in mice with POI. Mechanistically, it was found that Irisolidone suppressed abnormal ovarian inflammation by inhibiting the CTX-disrupted nuclear factor kappa B (NFκB)/NOD-like receptor pyrin domain-containing 3 (NLRP3)/Caspase1 signaling pathway. The present study demonstrates that Irisolidone can effectively alleviate CTX-induced POI by inhibiting abnormal inflammation. These findings suggest that Irisolidone holds promise as a novel therapeutic candidate for POI, thereby providing a potential new treatment strategy for clinical management of this condition.

Honokiol, a natural polyphenol from Magnolia bark, exhibits antitumor effects in various cancers. This study aimed to elucidate its pharmacological mechanisms in gastric cancer. Active components and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and SwissTargetPrediction databases. Gastric cancer-related genes were collected from the Comparative Toxicogenomics Database and GeneCards databases. Overlapping targets were analyzed using STRING to construct a protein–protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using DAVID and visualized using Cytoscape. Thirty-four overlapping targets were identified, with CHUK as a key hub gene. Functional enrichment analysis revealed multiple pathways, including NF-κB signaling. Single-cell analysis confirmed CHUK expression in tumor clusters, and immunohistochemistry validated its downregulation following honokiol treatment. These findings suggest that honokiol exerts multi-target and multi-pathway effects in gastric cancer, with CHUK-mediated inhibition of NF-κB signaling identified as a critical mechanism.

Background:Polycystic ovary syndrome (PCOS) is a polygenic multifactorial systemic inflammatory autoimmune disease. Mulberry twig (MT) has pharmacological activities such as anti-inflammatory, hypoglycemic, anti-oxidant, and insulin resistance. Our study aimed to understand whether MT can affect PCOS and to assess its potential targets.Methods:PCOS targets were searched using the OMIM, TTD, and GeneCards databases. The active components and corresponding protein targets of MT were searched in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the compound-target network was constructed using Cytoscape 3.8.0. The intersection of the compound and disease targets was obtained, and the coincidence target was imported into the STRING database to construct a protein–protein interaction (PPI) network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these targets. Finally, molecular docking methods were used to confirm the high affinity between the bioactive molecules of MT and their targets in PCOS.Results:TCMSP database results showed that the 3 active components of MT acted against PCOS. The PPI network and core target analysis suggested that AKT1, TNF, and CASP3 are key targets of PCOS. KEGG analysis showed that MT treatment in PCOS mainly involved fluid shear stress and atherosclerosis. GO analysis showed that positive regulation of the apoptotic process, caveola, and enzyme binding play an important role in MT in PCOS. Molecular docking methods confirmed the high affinity between the bioactive molecules of MT and their targets in PCOS.Conclusion:MT may serve as a promising therapeutic candidate for PCOS, as verified by the network pharmacology approach based on data mining and molecular docking methods. However, further in vivo and in vitro experiments are needed.

To examine the potential mechanisms of Yishenqingzhuo oral liquid (YSQZ) as a treatment for chronic kidney disease (CKD). The Traditional Chinese Medicine Systems Pharmacology and HERB databases were used to identify active ingredients and targets of YSQZ, and the GEO database was employed to screen CKD-related targets. Protein–protein interaction networks and enrichment analysis was conducted. Core targets and ingredients were identified from the protein–protein interaction network. Immune infiltration analysis was performed, and core targets and ingredients were validated via molecular docking. There were 97 active ingredients, 479 drug-predicted targets, 185 potential targets that were the same among the 479 drug-predicted targets and the 7193 CKD-related targets, 98 potential targets with interactions, and enrichment of 165 drug-related pathways. The topological analysis identified 29 core targets and 62 core ingredients. tumor protein 53, estrogen receptor 1, cyclin-dependent kinase 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta, mitogen-activated protein kinase 1 , and mitogen-activated protein kinase 3 were the key targets, and quercetin, caffeic acid, aloe-emodin, kaempferol, and palmatine were the core ingredients. Immune infiltration analysis showed that memory B cells, naive B cells, and activated NK cells differed markedly between the CKD and normal groups. YSQZ is hypothesized to act on CKD through multiple ingredients targeting multiple genes and signaling pathways. However, these findings are based on 1 GEO dataset with a relatively small sample size. Further experimental and clinical validation is needed to confirm the proposed mechanisms.

Investigating the potential anti-cancer mechanism for thyroid cancer: Role of Herba Epimedii via network pharmacology approach

Background and Objectives: This study employed an integrated approach combining network pharmacology and bioinformatics to systematically elucidate the multitarget mechanisms of tetramethylpyrazine (TMP) in ameliorating myocardial ischemia-reperfusion injury (MIRI), with a specific focus on its potential association with ferroptosis regulation. Methods: The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), PharmMapper, SwissTarget Prediction, and TargetNet databases were used to combine the data, which were subsequently used to identify TMP-related targets. Ferroptosis-associated targets were retrieved from the FerrDb database, whereas MIRI-related targets were screened via the GeneCards and DisGeNET databases. Venn diagram analysis was applied to identify overlapping targets among TMP, ferroptosis, and MIRI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation pathway enrichment analyses were conducted via R software to elucidate the underlying mechanisms involved. The protein-protein interaction (PPI) network was constructed via the STRING database, and topological analysis was performed via Cytoscape software to identify key targets. AutoDock Vina and PyMol were used to validate molecular docking. For experimental validation, an in vitro MIRI model was established using H9C2 cardiomyocytes subjected to hypoxia/reoxygenation (4h/2h). The cells were treated with 20 μM TMP or the ferroptosis inhibitor ferrostatin-1 (Fer-1, 20 μM). Intracellular reactive oxygen species (ROS) levels were detected using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and visualized by fluorescence microscopy, while the expression of the key ferroptosis-related protein GPX4 was assessed by Western blotting. Results: Twenty shared targets linked to ferroptosis were identified. Molecular docking validation revealed four important targets, namely, PPARG, MDM2, SIRT1, and GSK3B, which have favorable binding affinities for TMP (binding energy < -5.0 kcal/mol). The GO analysis indicated that TMP primarily regulates biological processes such as positive modulation of protein phosphorylation and activation of the MAPK cascade. The KEGG enrichment analysis highlighted key pathways, including proteoglycan (PG) signaling in cancer, lipid metabolism dysregulation, and efferocytosis. Consistently, in vitro experiments demonstrated that TMP treatment significantly attenuated the ischemia-reperfusion (I/R)-induced overproduction of ROS and counteracted the downregulation of GPX4 protein expression, exhibiting a protective effect comparable to Fer-1. Conclusions: These results suggest that TMP may reduce MIRI via synergistic and multipathway mechanisms, which may be related to the regulation of ferroptosis. Furthermore, this study provides new theoretical knowledge about the cardioprotective properties of TMP by validating its anti-inflammatory efficacy.

BackgroundKushe tincture (KSD), an optimized in-hospital preparation of Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, has been clinically used as an anti-inflammatory and anti-itching topical therapeutic drug for the treatment of eczema, atopic dermatitis (AD) and so on for decades. However, the potential therapeutic mechanisms remained unexplored.ObjectiveThis study aimed to explore the mechanisms underlying the therapeutic effects of KSD against DNCB-induced AD through the combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and animal experiments.MethodsFirstly, we collected the active components and targets of KSD from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and obtained AD-associated targets from the Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) networks were constructed using Cytoscape with Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Secondly, core targets were screened and visualized by scRNA-seq and ST technology. Finally, we adopted DNCB-induced AD-like mouse model to observe the therapeutic effect of KSD through lesion scoring, morphological staining, serological tests, skin barrier function measurements, flow cytometry, and Western blotting.ResultsForty-six common drug-disease targets were obtained and top 2 ranked targets were chosen, namely NF-kB1 and STAT3. Combined scRNA-seq and ST suggested that NF-KB and STAT3 had higher and wider expression in most subpopulations, especially in monocytes and CD4+ T-cells. Animal experiments showed that KSD treatment improved the visible symptoms and skin barrier function and decreased mast cell infiltration, IgE levels, Th17 cells, and expression of NF-kB, JAK2, and STAT3.ConclusionKSD has therapeutic effects on DNCB-induced AD-like skin lesions, and it has effects on NF-kB and JAK-STAT3 proteins, which may be possible targets.

Integrative computational-experimental discovery of α-hederin as a multi-mechanistic, low-toxicity antifungal agent targeting Candida albicans CYP51.

Astragalus membranaceus has shown positive clinical efficacy in treating colorectal cancer (CRC). This study aimed to identify the key active components of Astragalus and determine effective targets of these components in CRC patients. We identified active components of Astragalus membranaceus and differentially expressed genes in traditional Chinese medicine systems pharmacology database and The Cancer Genome Atlas. Additionally, the enrichment analysis of differential target genes (DTGs) was performed using the R-package clusterProfiler. Immunocyte correlation analysis and non-coding regulatory network construction were performed for biomarkers using Spearman's method and NetworkAnalyst. Finally, molecular docking of biomarkers and their corresponding molecule drugs was done with Autodock Vina software. We identified 20 active components of Astragalus membranaceus and 1 403 target genes through screening. A total of 2 300 differentially expressed genes, and 3 035 hub genes in CRC were screened. The integration of the target genes with the significantly differentially expressed genes and Hub genes identified resulted in a total of 86 DTGs. Subsequently, the results showed 828 enriched GO biological processes, 184 enriched GO molecular functions, 59 enriched GO cellular components, and 46 enriched KEGG pathways. We also obtained a total of 143 PPI pairs involving 67 nodes. Additionally, we constructed 45 mRNA-TF pairs, 101 miRNA-mRNA pairs, and 200 miRNA- mRNA-TF triplets. Finally, molecular docking was performed for the active component quercetin with F2 and UGT1A1 and formic acid with FGA, AHSG, and KNG1. This study identified the active components of Astragalus membranaceus and their corresponding targets in CRC. These findings provide robust evidence for precision drug therapy in patients with CRC.

Multi-omics and experimental validation reveal the mechanism of DanxiaTiaoban decoction in treating atherosclerosis.

The aim of this study was to investigate the possible mechanism by which Cassiae Semen treats DR via network pharmacology and to validate this mechanism via in vitro experiments. The active ingredients and potential DR-related targets of Cassia Semen were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform and other disease-related databases. A protein‒protein interaction network for these common targets was subsequently established via the STRING database. Key active ingredients and core targets were selected through network topology analysis using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID database. In vitro experiments were designed to further validate the key active components and targets of Cassiae Semen identified by network pharmacology analysis. Twenty-one common targets were selected. Aloe-emodin (AE) was speculated to be the main active ingredient of Cassiae Semen in the treatment of DR. Cassiae Semen might act through various biological processes, including by regulating apoptosis, oxidative stress, and inflammation. In vitro, AE effectively inhibited lipopolysaccharide (LPS)-induced BV2 cell proliferation and downregulated the mRNA expression of M1 microglia-related genes (COX2, iNOS, TNF-α, IL-1β and IL-6). Furthermore, AE inhibited proinflammatory cytokine (TNF-α, IL-1β and IL-6) secretion and the expression of the inflammatory protein COX2 in LPS-stimulated BV2 cells. Network pharmacology and in vitro experiments revealed that AE, the key active component of Cassiae Semen, suppresses inflammation by inhibiting M1 microglial polarization, making it a potential therapeutic agent for DR.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21963-x.

Jiaotai Pill (JTP) is a Traditional Chinese Medicine (TCM) prescription that has demonstrated therapeutic effects against Type 2 Diabetes Mellitus (T2DM). However, its active antidiabetic components and underlying mechanism of action remain unclear. This study aimed to identify the bioactive components in JTP and elucidate their molecular targets and therapeutic pathways in T2DM. Chemical components of JTP were identified using ultra-high performance liquid chromatography coupled with Q-Exactive Orbitrap high-resolution mass spectrometer (UHPLC-Q-Exactive Orbitrap-HRMS) in both positive and negative ion modes. Data were processed with Compound Discoverer 3.2 (CD 3.2) data software and validated using literature sources. Network pharmacology analysis was performed via multiple databases, including the Traditional Chinese Medicine Systems Pharmacology Database, Uniport, PubChem, GenCards, String, and Cytoscape, to predict potential bioactive compounds and therapeutic targets. Key interactions were validated using molecular docking and molecular dynamics simulations. A total of 104 compounds were identified in JTP. Network pharmacology analysis revealed 5 key antidiabetic components and 5 core targets. These targets are involved in biological processes including apoptosis regulation, cell proliferation, and protein phosphorylation, and are enriched in pathways such as neuroactive ligand-receptor interaction, PI3K-AKT signaling, and AGE-RAGE signaling. Molecular docking indicated strong binding affinity between dihydrochelerythrine and AKT1(-9.0 kcal/mol) and TNF-α (-6.7 kcal/mol). Molecular dynamics simulation demonstrated stable and sustained hydrogen bonding between dihydrochelerythrine and AKT1. Dihydrochelerythrine, as an active ingredient in JTP, may exert its antidiabetic mechanism by binding with AKT1, but it needs to be verified by subsequent animal or cell experiments. Dihydrochelerythrine, a key active component of JTP, may exert antidiabetic effects in T2DM through stable interaction with AKT1, highlighting a potential therapeutic mechanism.

Abstract Background: Intestinal obstruction is a prevalent complication in patients with colorectal cancer following surgery, with a significant impact on health outcomes. Dachengqi decoction (DCQD) is a traditional Chinese medicine (TCM) that is employed in clinical settings for the treatment of intestinal obstruction. However, the pharmacological mechanisms and active components of this medicinal preparation remain to be fully elucidated. The objective of this study was to examine the possible mechanisms and active constituents of DCQD in addressing intestinal obstruction subsequent to colorectal cancer surgery. Methods: A comprehensive search was conducted on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Traditional Chinese Medicine Integrated Database for the active chemical constituents of DCQD. In addition, the PubChem, Swiss Target Prediction and Uniprot databases were utilised to predict the drug targets. The possible target genes associated with intestinal obstruction were obtained from the GeneCards, Online Mendelian Inheritance in Man, PharmGKB, and Therapeutic Target Database databases, and were analysed using the Database for Annotation, Visualisation and Integrated Discovery platform for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Cytoscape was utilised to visualise key components, targets, and pathways, and molecular docking technology was employed to verify the binding of core targets and key components. Results: A total of 41 active chemical components and 141 intersecting targets were screened, and it was determined that the intersecting targets of TCM and disease were significantly enriched in 44 GO entries and 93 KEGG pathways. Subsequent screening identified 3 key components (isosinensetin, tetramethoxyluteolin, and 5,7,4’-trimethylapigenin) and 9 core targets ( TP53, STAT3, ESR1, SRC, EGFR, AKT1, CTNNB1, BCL2 , and PIK3CA ). The molecular docking results demonstrated that all 3 key components exhibited strong binding to the core targets. Conclusions: The present study identified the pharmacological basis by which DCQD exerts beneficial effects against intestinal obstruction and provided insights into its mechanism of action, providing scientific evidence for precise clinical utilisation and areas for new drug development.