Correction to “Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy”

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

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.

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.

Background Asthma is a chronic inflammatory disease of the airways with recurrent attacks, which seriously affects the patients' quality of life and even threatens their lives. The disease can even threaten the lives of patients. Sijunzi decoction (SJZD), a classical Chinese medicine formula with a long history of administration, is a basic formula used for the treatment of asthma and demonstrates remarkable efficacy. However, the underlying mechanism has not been elucidated. Materials and Methods We aimed to integrate network pharmacology and intestinal flora sequencing analysis to study the mechanism of SJZD in the treatment of allergic asthmatic mice. The active compounds of SJZD and their asthma-related targets were predicted by various databases. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify potentially relevant pathways for target genes. Furthermore, the active compound-target and target-signaling pathway network maps were constructed by using Cytoscape 3.8.2. These results were combined with those of the intestinal flora sequencing analysis to study the influence of SJZD on airway inflammation in allergic asthmatic mice. Result We obtained 137 active compounds from SJZD and associated them with 1445 asthma-related targets acquired from the databases. A total of 109 common targets were identified. We visualized active compound-target and target-signaling pathway network maps. The pathological analysis and inflammation score results suggested that SJZD could alleviate airway inflammation in asthmatic mice. Sequencing analysis of intestinal flora showed that SJZD could increase the relevant abundance of beneficial bacterial genus and maintain the balance of the intestinal flora. The core toll-like receptor (TLR) signaling pathway was identified based on network pharmacology analysis, and the important role TLRs play in intestinal flora and organismal immunity was also recognized. The analysis of the correlation between environmental factors and intestinal flora revealed that beneficial bacterial genera were negatively correlated with TLR2 and positively correlated with the TLR7 expression. Furthermore, they were positively correlated with IFN-γ and IL-10 levels and negatively correlated with IL-4 and IL-17 levels. Conclusion SJZD alleviated the airway inflammation state in asthmatic mice. The findings suggest that increasing the relevant abundance of beneficial intestinal bacteria in mice with asthma, regulating intestinal flora, interfering with the level of TLR2 and TLR7 expression to adjust the secretion of inflammatory factors, and alleviating asthmatic airway inflammation may be the possible mechanism involved in the treatment of asthma by SJZD, providing a basis for further studies on SJZD.

Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification. Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE’s laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing. Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP. Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.

Network pharmacology, molecular docking and experimental verification of the mechanism of huangqi-jixuecao herb pair in treatment of peritoneal fibrosis

The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while FN1 and PRKAA2 were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. In vivo experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.

Mechanism investigation of anti-NAFLD of Shugan Yipi Granule based on network pharmacology analysis and experimental verification

BackgroundHepatic ischemia-reperfusion injury (HIRI) is a major complication in clinical situations such as liver transplant, hypovolemic shock, and severe trauma, critically affecting patient prognosis. Therapeutic interventions targeting HIRI are limited....

Ionizing radiation (IR) can cause radiation damage, mutagenesis, or carcinogenesis in the irradiated subject. It is manifested as metabolic disorders of the body and damage to the immune system, nervous system, and endocrine system, which can lead to physiological and pathological changes and endogenous metabolic disorders. Ginsenoside Re (G-Re), a single component of traditional Chinese medicine, has a certain ameliorating effect on radiation damage. However, its mechanism of action in the treatment of radiotherapy injury remains unclear. With this purpose, the hematopoietic function of mice damaged by X-ray radiation was studied, and the protective effect of G-Re on mice damaged by radiation was preliminarily evaluated. Network pharmacology and metabolomics analysis are used to further reveal the mechanism of G-Re to improve radiation damage through metabolomics research. Results of metabolomics analysis showed that 16 potential biomarkers were identified as participating in the therapeutic effect of G-Re on IR. Most of these metabolites are adjusted to recover after G-Re treatment. The pathways involved included glycerophospholipid metabolism, sphingolipid metabolism, and linoleic acid metabolism. According to network pharmacology analysis, we found 10 hub genes, which is partly consistent with the findings of metabolomics. Further comprehensive analysis focused on 4 key targets, including SRC, EGFR, AKT1, and MAPK8, and their related core metabolites and pathways. This study combines metabolomics and network pharmacology analysis to explore the key targets and mechanisms of G-Re in the treatment of IR, in order to provide new strategies for clinical treatment of radiotherapy injury.

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.

Melanoma is a cutaneum carcinoma caused by the malignant transformation of melanocytes. This study aimed to predict potential targets of berberine in melanoma treatment and its mechanism of action through a network pharmacological analysis. The GeneCards databases and SwissTargetPrediction yielded five overlapped targets, including RAC1, CDK4, KIT, and CHEK2. The components-targets network diagram indicated that berberine interacted with the targets. The molecular docking showed that berberine exhibited a high binding affinity with all five targets and bound to them through hydrogen bonding and hydrophobicity. Furthermore, gene ontology enrichment analysis revealed that these targets were primarily involved in the hepatocyte growth factor receptor signaling pathway, followed by positive regulation of microtubule polymerization. The PI3K-Akt, Rap1, and Ras signaling pathways were the most significant influences in the Kyoto Encyclopedia of Genes and Genome analysis. This study predicted that berberine may be involved in the hepatocyte growth factor receptor signaling pathway and the PI3K-Akt signaling pathway in melanoma through MET, RAC1, CDK4, KIT, and CHEK2 through network pharmacological methods.

Pharmacodynamic substances in Salvia miltiorrhiza for prevention and treatment of hyperlipidemia and coronary heart disease based on lipidomics technology and network pharmacology analysis

Background: Atherosclerosis (AS) serves as the primary pathological foundation for numerous cardiovascular diseases, such as thromboembolic conditions, coronary artery disease, and ischemic cardiac-cerebral vascular disorders. Sanzi San, a traditional Chinese medicinal formulation with a long-standing clinical reputation for efficacy against AS, has not yet had its pharmacological mechanisms fully elucidated. Objective: Our objective is to investigate the impact of Sanzi San on AS in ApoE−/− mice models and elucidate the pharmacological mechanism via an integrated approach of serum pharmacochemistry, network pharmacology, and pharmacokinetic analysis. Materials and Methods: The chemical constituents in Sanzi San and serum were identified using high-performance liquid chromatography-quadrupole/Orbitrap high-resolution mass spectrometry (HPLC-Q/Orbitrap HRMS). A network pharmacology approach, including protein–protein interaction (PPI) and gene ontology enrichment analyses, was then used to investigate the connection between these components and their anti-atherosclerotic activity. Finally, ultra-HPLC-tandem mass spectrometry was used to determine the formula’s pharmacokinetic parameters following oral administration. Results: Through a comparison of serum samples from control and treated groups, 41 prototype compounds originating from Sanzi San were identified. These constituents were classified into three major groups – terpenes, iridoids, and phenolic acids – and were regarded as the potential bioactive components due to their absorption into the bloodstream. Network pharmacology analysis indicated that Sanzi San directly influences blood vessels by regulating their diameter to achieve therapeutic effects. Furthermore, Sanzi San demonstrated therapeutic potential by specifically targeting natural killer (NK) cells within plaque tissue and adventitial cells in the aorta. In vivo validation in ApoE−/− mice showed that Sanzi San improved aortic lesions and regulated body weight. Pharmacokinetic studies also revealed that seven major components of Sanzi San were present in plasma, confirming its pharmacological effects on AS. Conclusion: This study provides evidence of Sanzi San’s clinical efficacy in treating AS. The integrated strategy combining serum pharmacochemistry, network pharmacology, and pharmacokinetics offers a powerful approach for uncovering the key pharmacological mechanisms of herbal formulations.

Polygala fallax Hemsl (PFH) is a widely used herbal medicine in Guangxi, China. At present, research on PFH mainly focuses on extraction technology and cultivation, lacking quality control standards for systematic evaluation. The study aimed to assess the quality of PFH from different sources and to predict markers that would help assess quality. Fingerprinting of 15 batches of PFH samples was performed by ultra-high performance liquid chromatography (UPLC) and similarity was assessed using hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares discrimination (OPLS-DA). Differential components were screened by mathematical analysis, and a "component-target-pathway" network map was constructed in combination with network pharmacology, quality markers (Q-markers) of PFH were predicted, and quantitative analysis was performed. Fifteen batches were fingerprinted for PFH, with 11 common peaks, and peak 5 was identified as 4-hydroxybenzoic acid, which was generally consistent with the results of HCA, PCA, and OPLS-DA. Network pharmacology screened 18 potential compounds, 45 core targets, and 20 key pathways, integrating fingerprinting, pattern recognition, and network pharmacology methods. One of the potential Q-markers that can identify the principle of testability, efficacy, and specificity is 4-hydroxybenzoic acid, whose content ranges from 0.0188 to 1.4517 mg/g. The potential Q-markers of PFH were predicted by integrating fingerprinting, pattern recognition, and network pharmacological analysis, which provided a scientific basis for the overall control and evaluation of the quality of PFH and a theoretical reference for the study of the quality standard of multi-base traditional Chinese medicine.