An integrated approach for identifying the efficacy and potential mechanisms of TCM against atherosclerosis—Wu-Zhu-Yu decoction as a case study

Banxia Xiexin decoction (BXD) is a traditional prescription widely used to treat gastrointestinal conditions, including gastric cancer. Through network pharmacology, bioinformatics, and molecular docking analysis, this study aimed to investigate the potential mechanism of the antigastric cancer effect of BXD and pave the way for future research. The network pharmacology analysis used BXD index components to improve reliability and validity. Prognosis-related genes identified through Lasso and Cox regression analysis were considered potential BXD core targets for gastric cancer. Functional enrichment analysis was conducted to uncover the potential mechanism of action of BXD in gastric cancer. In addition, molecular docking of the index components of BXD and the core targets was used to validate the results. The present study obtained six index components of BXD and 155 corresponding antigastric cancer targets. ANXA5, CYP19A1, FGF1, and F2 in the prognostic signature model were identified as core targets of the index components of BXD. Protein-protein interaction networks and functional enrichment analysis indicated that proteoglycans in cancer, PI3K-Akt, and other pathways were involved. According to molecular docking results, six index components showed good-to-strong binding affinities to the core targets. The results indicated that the index components of BXD act on multiple pathways and targets of gastric cancer. Our study paved the way for further investigation of the antigastric cancer activity and mechanisms of BXD.

Gastrodia elata Blume (GEB) is widely used to treat cardio-cerebrovascular disease in China and in traditional Chinese medicine it is considered to be a dispelling wind and dredging collateral. However, the mechanism and active components of the plant in treating ischemic stroke (IS) remain unclear. The present study aimed to identify the active components and mechanism of GEB in treating IS using network pharmacology and molecular docking technology. Network analysis predicted 752 potential targets from 14 compounds in GEB, sharing 32 key targets with IS-associated targets. Gene Ontology analysis of key targets showed that 'oxidative stress', 'immune response' and 'regulation of blood circulation' were significantly enriched. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the key targets regulated 11 representative pathways including 'arachidonic acid metabolism', 'lipid and galactose metabolism'. In the protein-protein interaction network, five core targets, including toll-like receptor agonist, STAT3, myeloperoxidase (MPO), prostaglandin-endoperoxide synthase and matrix metalloproteinase (MMP)9, were identified and successfully docked with four active components: Palmitic acid, alexandrin, para-hydroxybenzaldehyde and gastrodin. Alexandrin, para-hydroxybenzaldehyde, and gastrodin are closely related to brain ischemia/reperfusion damage and repair. Therefore, to further verify the mechanism of action of three active components in the second part, we established the HT22 oxygen-glucose deprivation-reperfusion (OGD/R) model. Cell Counting Kit-8 assay and western blot analysis demonstrated that these three active components of GEB regulated core targets of molecular docking, such as STAT3, MPO and MMP9. In vitro experiments showed that OGD/R decreased cell survival, while this effect was reversed by the three active components of GEB. In addition, western blot analysis indicated that alexandrin upregulated expression of phosphorylated-STAT3, para-hydroxybenzaldehyde downregulated MPO and gastrodin downregulated MMP9. Therefore, the present study showed that GEB may prevent and treat IS via interaction between the active components and the main targets, which is key for investigating the efficacy of traditional Chinese medicine.

Although the protective effects of naringenin (Nar) on vascular smooth muscle cells (VSMCs) have been confirmed, whether it has anti-proliferation and anti-migration effects in high-glucose-induced VSMCs has remained unclear. This study aimed to clarify the potential targets and molecular mechanism of Nar when used to treat high-glucose-induced vasculopathy based on transcriptomics, network pharmacology, molecular docking, and in vivo and in vitro assays. We found that Nar has visible anti-proliferation and anti-migration effects both in vitro (high-glucose-induced VSMC proliferation and migration model) and in vivo (type 1 diabetes mouse model). Based on the results of network pharmacology and molecular docking, vascular endothelial growth factor A (VEGFA), the proto-oncogene tyrosine-protein kinase Src (Src) and the kinase insert domain receptor (KDR) are the core targets of Nar when used to treat diabetic angiopathies, according to the degree value and the docking score of the three core genes. Interestingly, not only the Biological Process (BP), Molecular Function (MF), and KEGG enrichment results from network pharmacology analysis but also transcriptomics showed that phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) is the most likely downstream pathway involved in the protective effects of Nar on VSMCs. Notably, according to the differentially expressed genes (DEGs) in the transcriptomic analysis, we found that cAMP-responsive element binding protein 5 (CREB5) is a downstream protein of the PI3K/Akt pathway that participates in VSMCs proliferation and migration. Furthermore, the results of molecular experiments in vitro were consistent with the bioinformatic analysis. Nar significantly inhibited the protein expression of the core targets (VEGFA, Src and KDR) and downregulated the PI3K/Akt/CREB5 pathway. Our results indicated that Nar exerted anti-proliferation and anti-migration effects on high-glucose-induced VSMCs through decreasing expression of the target protein VEGFA, and then downregulating the PI3K/Akt/CREB5 pathway, suggesting its potential for treating diabetic angiopathies.

Ovarian cancer was one of the gynecological malignant tumors. Salvia miltiorrhiza Bunge (SMB) was a kind of herbal medicine with an antitumor effect. However, the inhibitory effect of SMB on ovarian cancer and its potential mechanism were still unclear. The antitumor effect of SMB on ovarian cancer was studied by network pharmacology and molecular docking techniques, and its possible molecular mechanisms were analyzed. The active ingredients of SMB and the target data of ovarian cancer were obtained from the Traditional Chinese Medicines for Systems Pharmacology Database (TCMSP) and the GeneCards database. The relationship between active ingredients of SMB and ovarian cancer targets was analyzed by String database, David 6.8 online database, and Cytoscape 3.7.2 software, and then potential pathways were screened out. In addition, molecular docking technology was used to verify further the binding effect of antiovarian cancer pathway targets with active ingredients of SMB. Finally, survival analysis was performed for all potential targets. We analyzed 71 SMB-ovarian cancer common targets, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the PI3K-Akt signaling pathway might be an essential pathway for SMB to inhibit ovarian cancer. Luteolin, Tanshinone IIA, and Cryptotanshinone in SMB might play an important role. HSP90AA1, CDK2, and PIK3CG might be potential targets of SMB in inhibiting ovarian cancer. Through network pharmacology and molecular docking analysis, we found that SMB might partially inhibit ovarian cancer by the PI3K-Akt signaling pathway. We believe that SMB might be a potential therapeutic agent for ovarian cancer patients.

Epimedii herba (EH) showed numerous activities and has the potential to treat periodontitis. However, the pharmacological mechanism has not been exhaustively elucidated. This study predicted the specific targets and mechanisms of EH to prevent and treat periodontitis. A traditional Chinese medicine system pharmacology database and analysis platform was used to screen key compounds of EH and their corresponding targets. Therapeutic Target Database and Comparative Toxicogenomics Database were used to identify targets related to periodontitis. Intersection targets were observed using a Venn diagram. The key components and corresponding protein targets of EH were searched. The intersection targets were obtained and then they were imported into the STRING database to construct a PPI network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Molecular docking between the screened chemical components of EH and key targets was performed using Discovery Studio 2019. The binding stability between components and target proteins was confirmed using molecular dynamics simulations. The binding stability between components and target proteins was confirmed using molecular dynamics simulations. Through network pharmacological analysis, 23 active compounds of EH were identified, including kaempferol and icariin. Based on GeneCards, GEO, and other databases, 3291 periodontitis-related genes were obtained. Venn diagram analysis revealed 137 intersection targets of EH and periodontitis, and Protein kinase B (AKT1) and Tumor necrosis factor (TNF) were identified as the key targets of EH for periodontitis treatment. GO and KEGG analyses revealed that the primary pathways mediating the therapeutic effects of EH were related to cancer, lipid, and atherosclerosis. Molecular docking showed that 8-isopentenyl-kaempferol had the best binding ability to ESR1, which was confirmed by dynamics simulations. This study demonstrated that EH can be used for periodontitis treatment, and the corresponding targets and potential mechanisms were investigated based on network pharmacology, molecular docking, and dynamics simulation analysis. Notably, 8-isopentenyl-kaempferol exhibited good binding affinity and stability to ESR1, which may partially explain the molecular mechanisms of EH for treating periodontitis. Hence, EH can be a novel choice for the clinical treatment of periodontitis in the future.

Context: Breast cancer therapy currently presents several uncomfortable side effects in patients, including effects on non-malignant tissues, recurrence, and resistance, which restrict their utilization. Consequently, researchers have directed their attention toward studying plant-derived anticancer compounds that exhibit high efficacy and safety profiles. Eugenol, a major component found in clove plants, demonstrates promising potential as a therapeutic agent for both estrogen receptor-positive and estrogen receptor-negative breast cancer. Aims: To predict the target of eugenol in estrogen receptor–positive breast cancer using network pharmacology and molecular docking analyses. Methods: Network pharmacology analysis was performed using the Chemical Toxigenomic Database, STITCH, GeneCards, Cytoscape, Enrichr, and Stringdb. Subsequently, molecular docking was performed using protein targets obtained from the RCSB-PDB and analyzed using AutoDock software. Results: Network pharmacology study and molecular docking revealed the anticancer effect of eugenol against breast cancer estrogen receptor–positive, especially in cancer and apoptotic pathways, by acting on caspase-3 (CASP3), epidermal growth factor receptor (EGFR), and poly [ADP-ribose] polymerase 1 (PARP1) signaling pathways. The docking results between the protein targets and eugenol showed that eugenol has the strongest binding with CASP3 (ligand binding energy: -5.78 kcal/mol), followed by eugenol binding with EGFR (ligand binding energy: -5.58 kcal/mol), and eugenol binding with PARP1 (ligand binding energy: -5.58 kcal/mol). Conclusions: Eugenol is a potential candidate for breast cancer therapy, especially for apoptosis mediated by CASP3 in breast cancer luminal A.

We conducted network pharmacology and molecular docking analyses, and executed in vitro experiments to assess the mechanisms and prospective targets associated with the bioactive components of Bombyx batryticatus in the treatment of diabetic kidney disease (DKD). The bioactive components and potential targets of B batryticatus were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Using 5 disease databases, we conducted a comprehensive screening of potential disease targets specifically associated with DKD. Common targets shared between the bioactive components and disease targets were identified through the use of the R package, and subsequently, a protein-protein interaction network was established using data from the STRING database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses pertaining to the identified common targets were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Molecular docking simulations involving the bioactive components and their corresponding targets were modeled through AutoDock Vina and Pymol. Finally, to corroborate and validate these findings, experimental assays at the cellular level were conducted. Six bioactive compounds and 142 associated targets were identified for B batryticatus. Among the 796 disease targets associated with DKD, 56 targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the involvement of these shared targets in diverse biological processes and signaling pathways, notably the PI3K-Akt signaling pathway. Molecular docking analyses indicated a favorable binding interaction between quercetin, the principal bioactive compound in B batryticatus, and RAC-alpha serine/threonine-protein kinase. Subsequently, in vitro experiments substantiated the inhibitory effect of quercetin on the phosphorylation level of PI3K and Akt. The present study provides theoretical evidence for a comprehensive exploration of the mechanisms and molecular targets by which B batryticatus imparts protective effects against DKD.

BackgroundMeat originating from the spent hen is an important source of poultry meat production; however, multiple factors cause the decline in the meat quality of spent hens. Chinese herbs have been widely used as medicine for a long time to prevent diseases and as nutrient supplements to improve the product quality. This experiment explored the effects of adding 1.0% Chinese herbal formula (CHF, including 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz.) for 120 d to the spent hens’ diet through metabolomics, network pharmacology, and microbiome strategies.ResultsThe results indicated that CHF supplementation improved the meat quality by reducing drip loss (P < 0.05), b* value (P = 0.058), and shear force (P = 0.099) and increasing cooked meat percentage (P = 0.054) and dry matter (P < 0.05) of breast muscle. The addition of CHF improved the nutritional value of breast muscle by increasing (P < 0.05) the content of C18:2n-6, n-6/n-3 polyunsaturated fatty acids (PUFA), total PUFA, PUFA-to-saturated fatty acids (SFA) ratio, and hypocholesterolemic-to-hypercholesterolemic ratio, and tending to increase serine content (P = 0.069). The targeted metabolomics analysis revealed that the biosynthesis of SFA, linoleic acid metabolism, fatty acid degradation, fatty acid elongation, and fatty acid biosynthesis pathways were enriched by CHF supplementation. Furthermore, the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabolism. The CHF supplementation increased the glutathione peroxidase level (P < 0.05) and upregulated gene expression related to the Nrf2 pathway (including HO-1, P < 0.05; Nrf2, P = 0.098; CAT, P = 0.060; GPX1, P = 0.063; and SOD2, P = 0.052) and lipid metabolism (including PPARγ, P < 0.05; SREBP1, P = 0.059; and CPT1A, P = 0.058). Additionally, CHF supplementation increased Firmicutes and decreased Bacteroidetes, Spirochaetes, and Synergistetes abundances (P < 0.05), which may contribute to better meat quality.ConclusionsOur results suggest that CHF supplementation improved the quality and nutritional value of meat, which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’ diets.Graphical

1-Ethoxycarbonyl-beta-carboline inhibits the M2 polarization of tumor-associated macrophages: A study based on network pharmacology and molecular docking analyses

Background:Heart failure (HF) is the most common cardiovascular disease in clinics. Processed Panax ginseng C.A. Mey. Products have significant therapeutic effects on HF. Therefore, it is of great significance to explore the mechanism of action of Processed Panax ginseng C.A. Mey. Products in the treatment of HF.Methods:The saponin-like constituents of 3 different ginseng preparations were characterized by UPLC/QE-MS and the identified saponin constituents were subjected to network pharmacological analysis. Protein–protein interaction analyses of the targets of different ginseng preparations for the treatment of heart failure (HF) were performed using the STRING database, Gene Ontology enrichment analyses and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the DAVID database, and the results of the network pharmacological analyses were validated using the Autodock software. Finally, the relative quantitative content of 5 major ginsenosides in 3 processed ginseng products was evaluated.Results:A total of 40 saponin compounds were identified based on mass spectrometry data. Network pharmacology and molecular docking analyses were used to predict the major targets of these sapions compounds and the key pathways mediating their anti-HF effects. After conducting a thorough screening, the study identified 5 primary ingredients of ginseng products ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rk1, ginsenoside Rg5, and ginsenoside CK that can potentially target 22 essential proteins: EGFR, AKT1, ERBB2, STAT3, TNF, ESR1, MTOR, HRAS, MMP9, and PIK3CA, etc. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ginseng products can be beneficial in treating HF by interacting with pathways such as the PI3K-Akt signaling pathway, the TNF signaling pathway, the mTOR signaling pathway, and others.Conclusion:The present study revealed that the treatment of HF with different processed ginseng products may be related to the regulation of the PI3K-Akt signaling pathway, TNF signaling pathway, apoptosis pathway, mTOR signaling pathway, etc, and that the key active ingredients may be concentrated in black ginseng, which provides a theoretical basis and direction for the further study of the mechanism of action of ginseng. This provides a theoretical basis and research direction for further in-depth study of its mechanism of action.

Quality markers of Baizhu dispensing granules based on multi-component qualitative and quantitative analysis combined with network pharmacology and chemometric analysis

Lipidomics of the erythrocyte membrane and network pharmacology to explore the mechanism of mangiferin from Anemarrhenae rhizoma in treating type 2 diabetes mellitus rats

Intranasal administration of the essential oil from Perillae Folium ameliorates social defeat stress-induced behavioral impairments in mice

Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; β-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and β-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine