Can Epimedii herba treat periodontitis? A prediction based on network pharmacology, molecular docking, and dynamics analysis

To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.

This study aimed to explore the historical research progress on benign prostatic hyperplasia from the perspective of traditional Chinese medicine theory and the treatment of benign prostatic hyperplasia (BPH) with Qian Lie Xing Fang (QLXF) via the warming and tonifying of kidney yang, promotion of blood circulation, and clearing of meridians. First, network pharmacology analysis was used to screen and identify possible pathways for BPH treatment with QLXF. Subsequently, molecular docking analysis helped explore the mechanism of action by which the components of QLXF affected androgen receptor (AR) and type 5 phosphodiesterase inhibitor (PDE-5) levels. Targets for treatment with QLXF were identified from the online Mendelian inheritance in man and DisGeNET databases. BPH-related genes were identified using GeneCards and online Mendelian inheritance in man databases, and their intersection was used to construct a protein-protein interaction network analysis graph. Subsequently, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. The semiflexible docking of the ingredients of QLXF acting on the 2 targets was performed via molecular docking and molecular dynamics simulation, to elucidate the mechanism of action by which the active ingredients affect AR and PDE-5 levels further. This enabled us to explore the pattern of interactions between small active ingredient molecules, the target protein, and the stability after binding at the microscopic level. Gene ontology enrichment analysis showed that QLXF affected several processes, such as DNA transcription factor binding, kinase binding, protein homodimerization activity, protein structure domain-specific binding, and protein-coupled amine receptor activity in BPH patients. KEGG results showed that chemical carcinogenic reactive oxidative species and the JAK-STAT, Pl3k-Akt, FoxO, NF-κB, and other pathways were significantly enriched. Conducting molecular docking studies to investigate the interaction of active components from QLXF with AR and PDE-5, it was found that MOL002260 may possess the potential to inhibit PDE-5 activity, while MOL010578 may exhibit the capability to inhibit AR activity. QLXF is closely associated with various biological processes and KEGG signaling pathways related to BPH. The active ingredients of QLXF were investigated for their interactions with AR and PDE-5, with a primary focus on the small molecules MOL002260 and MOL010578.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

BackgroundTo use network pharmacology to explore the mechanism of the drug pair Rhubarb-Coptis in the treatment of diabetic nephropathy (DN).MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of drug pair Rhubarb-Coptis. Targets were obtained using the TCMSP and SwissTargetPrediction databases. DN disease targets were extracted from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target database (TTD) databases. A “drug-compound-target” network and protein-protein interaction (PPI) network were constructed and analyzed through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed using AutoDock Vina and PyMOL software.ResultsA total of 30 active components and 609 targets of Rhubarb-Coptis were screened out, and 98 common targets of DN and Rhubarb-Coptis were obtained. Quercetin, berberine, epiruberine, epautin, and moupinamide were the main active components in the treatment of DN. The STAT3, CTNNB1, PIK3R1, PIK3CA, and TP53 genes were identified as the potential 5 key targets. The GO enrichment analysis showed that these 5 key targets mainly involved in inflammation, oxidative stress, and apoptosis. KEGG enrichment analysis showed that the pathways were mainly enriched in the AGE-RAGE and HIF-1 signaling pathways. Molecular docking revealed that the 5 key targets could combine well with their corresponding active compounds.ConclusionsThis study expounds the therapeutic effect of Rhubarb-Coptis on DN from a holistic perspective, and provides a valuable basis for clinical application and academic research.

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.

Wuzi Yanzong Pill (WZYZP) is a traditional Chinese medicine formula extensively used in China to treat male reproductive dysfunction, with a specific focus on invigorating the kidney. Despite its observed efficacy, the exact mechanisms and therapeutic targets remain unclear. The primary goal of this study is to elucidate the potential molecular targets and underlying mechanisms of WZYZP in the treatment of asthenozoospermia (AZS). It will be achieved through the integration of network pharmacology and bioinformatics analyses in a comprehensive and systematic approach. This study employed bioinformatics analysis and network pharmacology methodologies, encompassing: construction of protein-protein interaction (PPI) networks; development of 'Ingredients-Potential Target Genes-Signaling Pathways' (IPS) networks; Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; differential gene analysis; molecular docking; and molecular dynamics simulations (MDS). Through network pharmacology analysis, we identified 485 potential targets of WZYZP. Cross-referencing with disease databases resulted in 57 intersecting targets pertinent to both WZYZP and AZS. Construction of the IPS network further determined eight core candidate targets: PIK3R1, MAPK3, GSK3B, AKT1, MAPK14, ESR1, ESR2, and CYP17A1. GO and KEGG pathway enrichment analyses highlighted significant involvement in prolactin signaling, endocrine resistance, and estrogen signaling pathways. Molecular docking and MDS confirmed stable binding of WZYZP components to all eight core targets. Our findings suggest that WZYZP may exert therapeutic effects in AZS by targeting eight pivotal genes (PIK3R1, MAPK3, GSK3B, AKT1, MAPK14, ESR1, ESR2, and CYP17A1). This is achieved through modulation of prolactin signaling, estrogen signaling, and endocrine resistance, thereby inhibiting inflammatory damage, antagonizing apoptotic signaling, maintaining hormonal homeostasis, and restoring metabolic imbalance.

Xiaoqinglong Decoction (XQLD) is a traditional Chinese medicinal formula commonly used to treat chronic urticaria (CU). However, its underlying therapeutic mechanisms remain incompletely characterized. This study employed an integrated approach combining network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations to identify the active components, potential targets, and related signaling pathways involved in XQLD's therapeutic action against CU, thereby providing a mechanistic foundation for its clinical application. The active components of XQLD and their corresponding targets were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CU-related targets were retrieved from the OMIM and GeneCards databases. Subsequently, core components and targets were determined via protein-protein interaction (PPI) network analysis and component-target-pathway network construction. Topological analyses were performed using Cytoscape software to prioritize core nodes within these networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database to identify enriched biological processes and signaling pathways. Molecular docking was performed to evaluate binding interactions between key components and core targets, while molecular dynamics (MD) simulations were employed to assess the stability of the component-target complexes with the lowest binding energy. Finally, CU-related targets of XQLD were validated using datasets from the Gene Expression Omnibus (GEO) database. A total of 135 active components and 249 potential targets of XQLD were identified, alongside 1,711 CU-related targets. Core components, such as quercetin, kaempferol, beta-sitosterol, naringenin, stigmasterol, and luteolin, exhibited high degree values in the constructed networks. The core targets identified included AKT1, TNF, IL6, TP53, PTGS2, CASP3, BCL2, ESR1, PPARG, and MAPK3. GO and KEGG pathway enrichment analyses revealed the PI3K-Akt signaling pathway as a central regulatory mechanism. Molecular docking studies demonstrated strong binding affinities between active components and core targets, with the stigmasterol-AKT1 complex exhibiting the lowest binding energy (-11.4 kcal/mol) and high stability in MD simulations. Validation using GEO datasets identified 12 core genes shared between CU-related targets and XQLD-associated targets, including PTGS2 and IL6, which were also prioritized as core targets in the network pharmacology analyses. This study comprehensively integrates multidisciplinary approaches to clarify the potential molecular mechanisms of XQLD in treating CU, highlighting its multitarget and multipathway synergistic effects. Molecular docking and dynamics simulations confirm the stable interaction between stigmasterol and the core target AKT1. Additionally, GEO dataset analysis verifies the pathogenic relevance of targets such as PTGS2 and IL6, significantly enhancing the credibility of our findings. These results provide a modern scientific basis for the traditional therapeutic effects of XQLD on CU and have important implications for developing multitarget treatments for this condition. However, this study mainly relies on database mining and computational simulations. Further in vitro and in vivo experimental validations are needed to confirm the predicted component-target-pathway interactions. This study identifies the active components, potential targets, and pathways through which XQLD exerts therapeutic effects on CU. These findings provide a theoretical foundation for further mechanistic studies and support their clinical application in the treatment of CU.

To explore the mechanism of Epimedii Folium (HF) and Notoginseng Radix (NR) intervention in vascular dementia (VD). This study used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database to collect the active ingredients and potential drug targets of HF and NR, the Uniprot database to convert drug target names into gene names, GeneCards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man database to collect the potential disease targets of VD, and then combined them with the drug targets to construct the HF-NR-VD protein-protein interaction (PPI) network by Search Tool for the Retrieval of Interacting (STRING). Cytoscape (version 3.7.1) was used to perform cluster analysis of the PPI network. Metascape database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The potential interaction of the main components of the HF-NR couplet medicine with core disease targets was revealed by molecular docking simulations. There were 23 predicted active ingredients in HF and NR, and 109 common drug targets that may be involved in the treatment of VD. Through PPI network analysis, 30 proteins were identified as core proteins owing to their topological importance. GO functional analysis revealed that the primary biological processes were mainly related to inflammation, apoptosis, and the response to oxidative stress. KEGG pathway enrichment analysis revealed that TNF and PI3K/Akt signaling pathways may occupy the core status in the anti-VD system. Molecular docking results confirmed that the core targets of VD had a high affinity for the main compounds of the HF-NR couplet medicine. We demonstrated the multi-component, multi-target, and multi-pathway characteristics of HF-NR couplet medicine for the treatment of VD and provided a foundation for further clinical application and experimental research.

To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome (CARAS) with lung–spleen qi deficiency and wind–cold invading the lung syndrome using network pharmacology and molecular docking.The active components and targets of the 13 herbs in Fuzheng Gankang Pill were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and HERB. A “core herb-active component–target” network was constructed using Cytoscape to screen core components. CARAS disease targets were obtained from Genecards, National Center for Biotechnology Information (NCBI), and Online Mendelian Inheritance in Man (OMIM). Targets related to the clinical phenotypes of CARAS with lung–spleen qi deficiency and wind–cold invading the lung syndrome were retrieved from the Traditional Chinese Medicine Syndrome Ontology and Multidimensional Quantitative Association Calculation Platform. The intersection of CARAS disease targets and syndrome-related targets yielded CARAS disease–syndrome targets. The intersection of Fuzheng Gankang Pill component-related targets and CARAS disease–syndrome targets provided “disease–syndrome–formula” intersection targets. These targets were uploaded to the STRING database for protein–protein interaction (PPI) network analysis, with topological analysis identifying key targets. Metascape was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking validation was performed using AutoDock Vina 1.1.2.The 13 core herbs of Fuzheng Gankang Pill contain a total of 200 active ingredients and 289 related targets. There are 2,412 disease targets for CARAS and 735 corresponding disease targets for the main and secondary symptoms of lung–spleen qi deficiency and wind–cold invading the lung. Through the Venn diagram, a total of 35 intersecting targets were obtained for Fuzheng Gankang Pill, CARAS, and the combination of lung–spleen qi deficiency and wind–cold invading the lung syndrome. Quercetin, Polygonatum sibiricum flavonoids, β-sitosterol, baicalein, kaempferol, etc., are core components. PPI network analysis found that tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin (IL)-1β, IL-6, transforming growth factor beta 1 (TGFβ1), BCL2, etc., are the core targets for the compound to exert therapeutic effects. GO enrichment analysis showed that the 13 core drugs of Fuzheng Gankang Pill mainly participate in key biological processes such as positive regulation of protein modification, response to hormones, and negative regulation of cell population proliferation through protein kinases in areas such as membrane rafts, membrane microregions, plasma membrane protein complexes, and receptor complexes. KEGG enriched a total of 30 signaling pathways. Molecular docking shows that active ingredients such as quercetin and kaempferol bind stably to TNF (binding energy ≤ −9.0 kcal·mol−1) and PTGS2 (≤ −8.5 kcal·mol−1).Fuzheng Gankang Pill may regulate biological processes such as cell apoptosis, tissue remodeling, inflammatory response, and immune response by acting on core targets such as TNF and PTGS2 through its core components quercetin, baicalein, β-sitosterol, baicalein, and kaempferol, thereby exerting therapeutic effects on CARAS with lung–spleen qi deficiency and wind–cold invading the lung syndrome.

Taohong Siwu decoction (THSWD) is a classic traditional Chinese medicine (TCM) formula known for its effects in promoting blood circulation, removing blood stasis, and rejuvenating energy. There have been clinical reports of THSWD treating chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel. We conducted a network pharmacology and molecular docking analysis to further clarify the molecular mechanisms by which THSWD exerts its protective effects against CIPN. Chemical components of THSWD and their corresponding targets were obtained through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and related targets of CIPN were searched in disease databases including Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), GeneCards, and DrugBank. Common targets between THSWD and CIPN were identified using Venn diagrams. A protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. AutoDock and PyMOL were used for the molecular docking validation of the key components of THSWD with core targets. At total of 69 chemical components of THSWD were identified, corresponding to 856 targets; 2,297 targets were associated with CIPN, with an intersection of 105 common targets. PPI analysis identified eight core targets: MYC, TNF, MAPK14, AKT1, ESR1, RELA, TP53, and HSP90AA1; KEGG enrichment analysis implicated signaling pathways such as PI3K-Akt, NF-κB, and HIF-1, etc. Molecular docking results indicated that the selected active components and their corresponding target proteins have good binding activity. Through network pharmacology, this study found that THSWD has significant advantages in treating CIPN. By analyzing potential core targets, biological functions, and involved signaling pathways, we clarified the potential molecular biological mechanisms involved in THSWD's treatment effect. This study provides a theoretical basis for the clinical application of THSWD in treating CIPN.

BackgroundTaraxacum mongolicum (TM) is a widely used herb. Studies have reported that TM exhibits growth-inhibitory and apoptosis-inducing on multiple tumors, including hepatocellular carcinoma (HCC). The active ingredients, targets, and molecular mechanisms of TM against HCC need to be further elucidated.MethodsWe identified the active ingredients and targets of TM via HERB, PubChem, SwissADME, SwissTargetPrediction, and PharmMapper. We searched HCC targets from GeneCards, Comparative Toxicogenomics Database (CTD), and DisGeNET. Then, the intersection of drug targets and disease targets was uploaded to the STRING database to construct protein-protein interactions (PPI) networking whose topology parameters were analyzed in Cytoscape software to screen hub targets. Next, we used Metascape for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and we employed AutoDock vina, AMBER18 and PyMOL software along with several auxiliary tools for molecular docking and molecular dynamics (MD) simulation. Finally, based on the in silico findings, cellular experiments were conducted to investigate the effect of TM on HSP90AA1 gene expression.ResultsA total of 228 targets and 35 active ingredients were identified. Twenty two hub targets were selected through PPI networking construction for further investigation. The enrichment analysis showed that protein kinase binding, mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were mainly involved. Molecular docking and MD simulation results supported good interaction between HSP90 protein and Austricin/Quercetin. The in vitro assay showed that TM inhibited the proliferation of HepG2 cells and the expression of HSP90AA1 gene.ConclusionsThis study is the first to use network pharmacology, molecular docking, MD simulation and cellular experiments to elucidate the active ingredients, molecular targets, and key biological pathways responsible for TM anti-HCC, providing a theoretical basis for further research.

To explore the mechanism of Hedyotis Diffusae Herba-Smilacis Glabrae Rhizoma(HDH-SGR) in treating lung adenocarcinoma based on big data bioinformatics combined with network pharmacology analysis and molecular docking technology. The chemical components and potential therapeutic targets of HDH-SGR were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Lung adenocarcinoma-related genes were obtained from The Cancer Genome Atlas(TCGA), Therapeutic Target Database(TTD), Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB), Online Mendelian Inheritance in Man(OMIM), DrugBank, and GeneCards. &quot;Drug component-target&quot; network was constructed using Cytoscape to screen out key compounds. STRING was used to build protein-protein interaction(PPI) network and core targets were screened out by Cytoscape-CytoNCA topology analysis. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses of target genes were performed by R-clusterProfiler. Finally, key compounds were docked to core target genes using AutoDock. The results showed that 22 active compounds and 499 potential therapeutic targets were obtained from HDH-SGR. A total of 14 332 lung adenocarcinoma-related targets were screened out through six data platforms, including 182 common targets. Fifteen core targets were screened out from the PPI network. GO and KEGG analyses revealed significant enrichment of relevant target genes in various biological processes, cellular functions(e.g., response to lipopolysaccharide, nuclear receptor activity, and ligand-activated transcription factor activity) and close relationship between target genes and non-small cell lung cancer signaling pathways. Based on the results of molecular docking validation, diosgenin, quercetin, naringenin, taxifolin, 2-methoxy-3-methyl-9,10-anthraquinone, stigmasterol, and β-sitosterol were able to bind tightly to the core targets. HDH-SGR can intervene in lung adenocarcinoma through multiple targets and signaling pathways, such as non-small cell lung cancer signaling pathways. The binding of active components in Chinese medicine to key targets is presumedly one of the mechanisms that produce therapeutic effects.

Baihe Zhimu decoction (BZD) has significant antidepressant properties and is widely used to treat mental diseases. However, the multitarget mechanism of BZD in postpartum depression (PPD) remains to be elucidated. Therefore, the aim of this study was to explore the molecular mechanisms of BDZ in treating PPD using network pharmacology and molecular docking. Active components and their target proteins were screened from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The PPD-related targets were obtained from the OMIM, CTD, and GeneCards databases. After overlap, the targets of BZD against PPD were collected. Protein-protein interaction (PPI) network and core target analyses were conducted using the STRING network platform and Cytoscape software. Moreover, molecular docking methods were used to confirm the high affinity between BZD and targets. Finally, the DAVID online tool was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping targets. The TCMSP database showed that BZD contained 23 active ingredients in PPD. KEGG analysis showed that overlapping genes were mainly enriched in HIF-1, dopaminergic synapses, estrogen, and serotonergic synaptic signalling pathways. Combining the PPI network and KEGG enrichment analysis, we found that ESR1, MAOA, NR3C1, VEGFA, and mTOR were the key targets of PPD. In addition, molecular docking confirmed the high affinity between BZD and the PPD target. Verified by a network pharmacology approach based on data mining and molecular docking methods, the multi-target drug BZD may serve as a promising therapeutic candidate for PPD, but further in vivo/in vitro experiments are needed.

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.

BackgroundAsiaticoside (AS) is a saponin extracted from the traditional Chinese herbal medicine Centella Asiatica, which has the effects of reducing inflammatory infiltration and anti-oxidation in pneumonia and combating pulmonary fibrosis. We hypothesize that AS might have therapeutic potential for the treatment of the coronavirus disease 2019 (COVID-19). With the help of network pharmacology and molecular docking techniques, this study discussed the underlying molecular mechanism of AS in the treatment of COVID-19.MethodsThe molecular structure of AS was obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) system. The targets of AS were achieved using PharmMapper, SwissTargetPrediction, and the Comparative Toxicogenomics Database (CTD). The targets corresponding to COVID-19 were obtained using GeneCards, Online Mendelian Inheritance in Man (OMIM), and CTD database. Then, a target protein-protein interaction (PPI) network was formed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. A network of AS, COVID-19, and their co-targets was built using Cytoscape. Afterwards, the co-targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Moreover, the predictions of crucial targets were further investigated by performing molecular docking with AS.ResultsA total of 45 core targets of AS were found to be engaged in the pathogenesis of COVID-19. The KEGG enrichment analysis indicated that AS might be protective against COVID-19 through inflammation- and immune-related signaling pathways, including interleukin-17 (IL-17) signaling, T helper 17 (Th17) cell differentiation pathway, Coronavirus disease-COVID-19, MAPK, the PI3K-Akt signaling pathway, and so on. The results of molecular docking showed that AS had a high affinity with those core targets.ConclusionsThe beneficial effect of AS on COVID-19 might be through regulating multiple immune or inflammation-related targets and signaling pathways.