Perspective Of Pharmacology Research Articles

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

Amentoflavone reverses epithelial-mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis.

Epithelial-mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone-regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK-8 kit, wound healing assay, Transwell assay and annexin V-FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V-FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.

Review of the textbook “Clinical and pharmacological characteristics of biotechnological drugs: from classifications to adverse events”

The European SocIn March 2024, the manual “Clinical and pharmacological characteristics of biotechnological drugs: from classifications to adverse events” was published under general ed. Kolbin A. S. This textbook discusses biotechnological drugs from the perspective of clinical pharmacology. Basic definitions and classifications are given. Pharmacodynamics, phar­macokinetics and adverse events are reviewed. Examples of interactions between biotechnological drugs and small molecules are presented. A separate chapter examines the interchangeability of biological products — from basic terms and definitions of the concept of biosimilarity to regulatory aspects. The Appendix provides examples of clinical applications of therapeutic proteins. The manual is intended for students, residents, graduate students, clinical pharmacologists and physicians of other specialties.

Review of the book “Practical issues of rational antibacterial therapy”

In 2023, the book “Practical Issues of Rational Antibacterial Therapy” under general ed. Yarovoy SK, Khokhlov AL, was published. This monograph is devoted to practical issues of empirical therapy for the most common nonspecific infectious and inflammatory diseases. The monograph presents the main provisions of antimicrobial therapy from the perspective of clinical pharmacology. The general patterns of prescription and distribution of antibacterial agents, the concepts of basic and reserve drugs, selection of hospital strains, natural and acquired resistance are explained. Antibacterial drugs are compared in pairs with each other based on an analysis of their spectra of antimicrobial activity. Combination (multicomponent) antibacterial therapy is being considered. Undesirable regimens of antimicrobial therapy are described, options with insufficient effectiveness and an unsatisfactory safety profile are analyzed.

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

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

Pharmacological underlying mechanisms of the anticancer effect of licorice: Bioinformatics and experimental verification

PurposeCancer is the second leading cause of human mortality and has rapidly become a major global issue. According to traditional Chinese medicine (TCM) theory, the primary pathogenesis of cancer is the deficiency of "vital Qi". Licorice (Gancao in Chinese, GC) one of the oldest and the most frequently used herbs for tonifying Qi, is commonly integrated with other Chinese medicines to treat cancer in TCM clinical practice. GC extract, or its chemical components, are often utilized in cancer treatment. However, the molecular mechanisms underlying GC's therapeutic effects on cancer remain unclear. Our current study aimed to elucidate these mechanisms from the perspective of network pharmacology and experimental validation. MethodsWe employed network pharmacology and bioinformatics to explore the anti-cancer mechanism, crucial targets, and kernel ingredients of GC. The significant targets and key ingredients (quercetin, glycyrrhetinic acid, and glucyrin) were substantiated using the Cancer Genome Atlas (TCGA) and Cell Counting Kit-8 (CCK-8) viability assay, respectively. ResultsOur findings identified eight critical targets and key ingredients (quercetin, glycyrrhetinic acid, glucyrin) and suggested that GC's anti-cancer effects are primarily associated with modulation of the immune system, signal transduction, cell cycle, and gene expression. The efficacy of quercetin, glycyrrhetinic acid, glucyrin against Human A549 lung cancer cells was confirmed. ConclusionThis study comprehensively elucidates the mechanisms through which GC addresses cancer, leveraging network pharmacology and experimental validation. These insights contribute to identifying principal compounds and developing innovative drugs for cancer therapy.

Preliminary discussion on the mechanism of active components of Radix Aconiti kusnezoffii in the treatment of migraine based on network pharmacology

To investigate the mechanism of action of Cao Wu in the treatment of migraine from the perspective of network pharmacology. The Swiss Target Prediction Database and CTD database were used to predict the target information of Cao Wu. Human Genome Database gene cards were used to find migraine-related target genes. The target protein interaction network and the “active ingredient-target” network were obtained by combining Cytoscape 3.7.1 software and R language. Enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes pathway and gene function analysis (GO) were performed using the R language to preliminarily explore the multiple pharmacological mechanisms of Radix Aconiti kusnezoffii. Forty-three indicators were identified. A total of 176 migraine targets were identified through the genecards database and OMIM database. Radix Aconiti kusnezoffii targets were compared with migraine targets and 12 overlapping targets were extracted. The protein interaction network of the overlapping targets was analyzed to identify the key targets for the drug to affect the disease. In addition, Kyoto Encyclopedia of Genes and Genomes pathway and go function enrichment analyses were performed on the overlapping targets to explore the therapeutic mechanism of migraine. The treatment of migraine with herbal woo is characterized by multi-component, multi-target, and multi-channel, which exerts complex network regulation through the interaction between different targets, providing a new idea and basis for further exploring the mechanism of action of herbal woo in the treatment of migraine.

Exploring the molecular mechanism of Licorice rose beverage anti-melasma based on network pharmacology, molecular docking technology and in vivo and in vitro experimental verification

Melasma is a pigmentation disease with refractory and high recurrence risk. Therefore, finding effective treatment has become the focus of research. This study aimed to reveal the mechanism of Licorice rose beverage (LRB) in treating melasma from the perspective of network pharmacology and in vitro and in vivo experimental techniques. Network pharmacological studies have shown that Isolicoflavonol, quercetin, and kaempferol are the main active components of anti-melasma and tyrosinase is the main target. Molecular docking studies have shown that these compounds have a good affinity for these targets. In vitro tyrosinase inhibition experiments showed that LRB could significantly inhibit tyrosinase activity. In vivo studies showed that LRB could significantly improve skin damage and skin pigmentation, reduce the activities of serum and skin tyrosinase in model mice, increase the activity of SOD in serum, and reduce the content of MDA in mice, showing a good effect of anti-melasma. In conclusion, these findings reveal the molecular mechanism of LRB in treating melasma and provide the scientific basis for this product's development and clinical application.

Digital Therapeutics as a New Therapeutic Modality: A Review from the Perspective of Clinical Pharmacology.

The promise of transforming digital technologies into treatments is what drives the development of digital therapeutics (DTx), generally known as software applications embedded within accessible technologies - such as smartphones - to treat, manage or prevent a pathological condition. While DTx solutions that successfully demonstrate effectiveness and safety could drastically improve the life of patients in multiple therapeutic areas, there is a general consensus that generating therapeutic evidence for DTx presents challenges and open questions. We believe there are three main areas where the application of clinical pharmacology principles from the drug development field could benefit DTx development: the characterization of the mechanism of action, the optimization of the intervention, and finally, its dosing. We reviewed DTx studies to explore how the field is approaching these topics and to better characterize the challenges associated with them. This leads us to emphasize the role that the application of clinical pharmacology principles could play in the development of DTx and to advocate for a development approach that merges such principles from development of traditional therapeutics with important considerations from the highly attractive and fast-paced world of digital solutions.

Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer's Disease through Network Pharmacology, Molecular Docking, and In Vivo Experiment.

Alzheimer's disease (AD) is the most common neurodegenerative disease, severely reducing the cognitive level and life quality of patients. Byu dMar 25 (BM25) has been proved to have a therapeutic effect on AD. However, the pharmacological mechanism is still unclear. Therefore, this study aims to reveal the potential mechanism of BM25 affecting AD from the perspective of network pharmacology and experimental validation. The potential active ingredients of BM25 were obtained from the TCMSP database and literature. Possible targets were predicted using SwissTargetPrediction tools. AD-related genes were identified by using GeneCards, OMIM, DisGeNET, and Drugbank databases. The candidate genes were obtained by extraction of the intersection network. Additionally, the "drug-target-disease" network was constructed by Cytoscape 3.7.2 for visualization. The PPI network was constructed by the STRING database, and the core network modules were filtered by Cytoscape 3.7.2. Enrichment analysis of GO and KEGG was carried out in the Metascape platform. Ledock software was used to dock the critical components with the core target. Furthermore, protein levels were evaluated by immunohistochemistry. In this study, 112 active components, 1112 disease candidate genes, 3084 GO functions, and 277 KEGG pathways were obtained. Molecular docking showed that the effective components of BM25 in treating AD were β-asarone and hydroxysafflor yellow A. The most important targets were APP, PIK3R1, and PIK3CA. Enrichment analysis indicated that the Golgi genetic regulation, peroxidase activity regulation, phosphatidylinositol 3-kinase complex IA, 5-hydroxytryptamine receptor complexes, cancer pathways, and neuroactive ligand-receptor interactions played vital roles against AD. The rat experiment verified that BM25 affected PI3K-Akt pathway activation in AD. This study reveals the mechanism of BM25 in treating AD with network pharmacology, which provides a foundation for further study on the molecular mechanism of AD treatment.

ChatGPT: First glance from a perspective of clinical pharmacology.

ChatGPT: First glance from a perspective of clinical pharmacology.

Ferroptosis in Rat Lung Tissue during Severe Acute Pancreatitis-Associated Acute Lung Injury: Protection of Qingyi Decoction.

Qingyi decoction (QYD) has anti-inflammatory pharmacological properties and substantial therapeutic benefits on severe acute pancreatitis (SAP) in clinical practice. However, its protective mechanism against SAP-associated acute lung injury (ALI) remains unclear. In this study, we screened the active ingredients of QYD from the perspective of network pharmacology to identify its core targets and signaling pathways against SAP-associated ALI. Rescue experiments were used to determine the relationship between QYD and ferroptosis. Then, metabolomics and 16s rDNA sequencing were used to identify differential metabolites and microbes in lung tissue. Correlation analysis was utilized to explore the relationship between core targets, signaling pathways, metabolic phenotypes, and microbial flora, sorting out the potential molecular network of QYD against SAP-associated lung ALI. Inflammatory damage was caused by SAP in the rat lung. QYD could effectively alleviate lung injury, improve respiratory function, and significantly reduce serum inflammatory factor levels in SAP rats. Network pharmacology and molecular docking identified three key targets: ALDH2, AnxA1, and ICAM-1. Mechanistically, QYD may inhibit ferroptosis by promoting the ALDH2 expression and suppress neutrophil infiltration by blocking the cleavage of intact AnxA1 and downregulating ICAM-1 expression. Ferroptosis activator counteracts the pulmonary protective effect of QYD in SAP rats. In addition, seven significant differential metabolites were identified in lung tissues. QYD relatively improved the lung microbiome's abundance in SAP rats. Further correlation analysis determined the correlation between ferroptosis, differential metabolites, and differential microbes. In this work, the network pharmacology, metabolomics, and 16s rDNA sequencing were integrated to uncover the mechanism of QYD against SAP-associated ALI. This novel integrated method may play an important role in future research on traditional Chinese medicine.

Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19

Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer value. Heparin-associated molecular targets and their mechanism of action in sepsis/COVID-19 are not well understood. In this work, we characterize the pharmacological targets, biological functions and therapeutic actions of heparin in sepsis/COVID-19 from the perspective of network pharmacology. A total of 38 potential targets for heparin action against sepsis/COVID-19 and 8 core pharmacological targets were identified, including IL6, KNG1, CXCL8, ALB, VEGFA, F2, IL10 and TNF. Moreover, enrichment analysis showed that heparin could help in treating sepsis/COVID-19 through immunomodulation, inhibition of the inflammatory response, regulation of angiogenesis and antiviral activity. The pharmacological effects of heparin against these targets were further confirmed by molecular docking and simulation analysis, suggesting that heparin exerts effective binding capacity by targeting the essential residues in sepsis/COVID-19. Prospective clinical practice evaluations may consider the use of these key prognostic indicators for the treatment of sepsis/COVID-19. Communicated by Ramaswamy H. Sarma

Molecular Mechanism of Qingchang Suppository in the Treatment of Ulcerative Colitis Based on Network Pharmacology

Objective: The study aims to explore the mechanism of Qingchang Suppository in the treatment of ulcerative colitis from the perspective of network pharmacology. Methods: The TCM Pharmacology database and analysis platform (TCMSP) were used to determine the effective components and related target information of the Qingchang Suppository. The main objective is to search the target genes related to ulcerative colitis using the GeneCards database. The target abbreviation is transformed into gene number by Perl language. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed by R language. The pharmacological mechanism of Qingchang supply was discussed, laying the foundation for the next experiment. Results: 869 indexes of Qingchang Suppository were determined. 368 targets of ulcerative colitis were obtained. Qingchang Suppository and ulcerative colitis were compared, and 141 overlapping targets were extracted. The "active ingredient target" network of Qingchang Suppository was constructed. The interaction between the effective components of Qingchang Suppository and the target of ulcerative colitis was revealed. The overlapping targets were analyzed for the KEGG pathway and function enrichment to explore the mechanism of Qingchang Suppository in the treatment of ulcerative colitis. Conclusion: Qingchang Suppository has the characteristics of multi-component, multi-target and multichannel, which provide a new idea and basis for further study on the mechanism of Qingchang Suppository in the treatment of ulcerative colitis.

Study on the Mechanism of Liuwei Dihuang Pill in Treating Hypothyroidism Based on Network Pharmacology

Objective: To study the mechanism of Liuwei Dihuang Pill (LWDP) in the treatment of hypothyroidism from the perspective of network pharmacology. Methods: The active ingredients of Liuwei Dihuang pill were screened by TCMSP platform database and the target prediction was carried out. GeneCards database was used to screen genes associated with hypothyroidism.The target of Liuwei Dihuang pill in treating hypothyroidism was obtained by Venny platform. The protein-protein interaction (PPI) network, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these targets were performed to reveal the possible mechanism of Liuwei Dihuang pill in treating hypothyroidism. Results: A total of 28 active components and 189 targets were identified from Liuwei Dihuang Pills, and 4502 targets were identified from GeneCard database. The PPI network contains 124 nodes and 323 edges. 662 biological processes (BP), 72 cell components (CC) and 127 molecular functions (MF) were obtained by GO enrichment. A total of 149 signaling pathways were obtained by KEGG enrichment analysis, and the top 20 signaling pathways were visualized and analyzed.The signal pathways related to hypothyroidism include AGE-RAGE signal pathway, lipid and atherosclerosis signal pathway, HIF-1 signal pathway, PI3K-Akt signal pathway and MAPK signal pathway. Conclusion: The main components of Liuwei Dihuang pill in treating hypothyroidism are quercetin, kaempferol, β-sitosterol, diosgenin, kadsurenone, hederagenin, sitosterol and stigmasterol. The main targets of Liuwei Dihuang pill are MAPK1, TP53, TNF, AKT1 and EGFR, and they play a therapeutic role through AGE-RAGE, lipid and atherosclerosis, HIF-1, PI 3K-Akt and MAPK signal pathways.

Mechanism of Banxia-Huanglian in the Treatment of Diabetes from the Perspective of Network Pharmacology Based on "Xin Kai Ku Jiang" Theory

Mechanism of Banxia-Huanglian in the Treatment of Diabetes from the Perspective of Network Pharmacology Based on "Xin Kai Ku Jiang" Theory

Mechanisms of JinHong Formula on treating sepsis explored by randomized controlled trial combined with network pharmacology

Ethnopharmacological relevanceJinHong Formula (JHF) was derived from the famous Rhubarb and Moutan Decoction which was prescribed for appendicitis. It was originally recorded in the classic of “Jingui Yaolve” written by Zhang Zhongjing. It is a kind of traditional Chinese medicine, widely used in the treatment of inflammation. However, the clinical effect of JHF for sepsis and its comprehensive mechanism in sepsis remained largely unknown. Research purposeThe aim of our study was to evaluate the clinical effect of JHF in the treatment of sepsis, and to explore its mechanism from the perspective of network pharmacology. Research methodsThe single-center randomized clinical trial was conducted to assess the effect of JHF in the treatment of sepsis. Additionally, we used the Chinese herbal medicine pharmacology database and analysis platform to identify the active components and therapeutic target of JHF. Numerous well-known disease target databases have been used to screen therapeutic target proteins for sepsis. Furthermore, we have established a Protein-Protein Interaction (PPI) network and carried out Gene Onotology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis. In order to conclude which active compounds from JHF may be responsible for signaling pathway, we performed network analysis. Research resultsThe study included 114 patients. By comparing participants with and without JHF, the results suggested that JHF significantly reduced all-cause mortality on 28 and 60 days after intervention, and improved Sequential Organ Failure Assessment (SOFA) on 7th day after intervention as well as. JHF had an effect of anti-inflammatories and antioxidants (SOD). By using network pharmacological analysis, we identified 72 active components and 426 target genes of JHF, and successfully constructed a “JHF-compound target-sepsis” network. 116 mentioned targets revealed by GO/KEGG enrichment analysis played a significant role in the inflammatory reaction and immunoregulation via interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathway. Moreover, the analysis of “pathway target-active component” revealed that Sennidin A, Rheidin A, Rheidin B, Rheidin C, (E)-4-Phenyl-3-Buten-2-One, Osmanthuside H, Esculetin, and Caffeicacid were responsible for IL-17, TNF signaling pathways. ConclusionJHF contains potential active substance of anti-inflammatory and antioxidant. These active compounds may come into play through IL-17 and TNF signaling pathways. For sepsis, JHF may be a promising and effective treatment strategy.

Effects and mechanisms of Xiaochaihu Tang against liver fibrosis: An integration of network pharmacology, molecular docking and experimental validation

Ethnopharmacological relevanceLiver fibrosis is a potentially harmful chronic liver disease caused by various etiologies. There is currently no specific drug for liver fibrosis. Xiaochaihu Tang (XCHT) is a traditional formula combined of seven herbs, which was first recorded in the Treatise on Febrile Diseases in Han Dynasty of ancient China. It is widely used in clinic to hepatic protection, analgesic, antipyretic and anti-inflammatory treatment. And it has been recommended for treating chronic hepatitis and chronic cholecystitis in the latest guidelines for the diagnosis and treatment of liver fibrosis with integrated traditional and western medicine. However, the underlying regulatory mechanisms remain elusive. Aim of the studyThis study aims to explore the therapeutic effects of XCHT on liver fibrosis and its underlying molecular mechanisms from the perspective of network pharmacology and experimental research. Materials and methodsCarbon tetrachloride (CCl4) induced and bile duct ligation (BDL) induced liver fibrosis models in mice were established to evaluate the anti-fibrosis effects of XCHT in vivo. Potential anti-fibrosis targets of XCHT were screened via network establishment. The underlying mechanisms were uncovered through GO and pathway enrichment analysis. Then, the core targets were identified from protein-protein interaction network by means of the Cytohubba plug-in of Cytoscape. Furthermore, two effective monomer components of XCHT were recognized by molecular docking. Moreover, the predicted components and pathways were verified by in vitro experiments. ResultsWhen treated with XCHT, liver fibrosis was alleviated in both mice models, showing as the improvement of liver function, the protection of hepatocytes, the inhibition of HSC activation and the reduction of hepatic collagen accumulation. 540 monomer components, 300 therapeutic targets, 109 signaling pathways, 246 GO biological processes, 77 GO cellular components, 107 GO molecular functions items and core targets were identified by network analysis. Then, 6-gingerol and baicalein were identified as the core components of anti-fibrosis effects of XCHT via leptin or Nrf2 signaling pathway. Furthermore, the experiment in vitro also validated the results. ConclusionsOur study suggests XCHT could alleviate liver fibrosis through multi-targets and multi-pathways; 6-gingerol and baicalein are its core components which may play an important role via leptin or Nrf2 signaling pathway.

Identification of Taohong Siwu Decoction in Treating Chronic Glomerulonephritis Using Network Pharmacology and Molecular Docking

Background: Based on network pharmacology and molecular docking technology, the pharmacological mechanism of Taohong Siwu Decoction (THSWD) in the treatment of chronic glomerulonephritis (CGN) was analyzed to provide a theoretical basis for the subsequent development of new drugs and the clinical application of Traditional Chinese Medicine (TCM). Methods: Active ingredients of drugs and disease target genes were obtained from Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database and GeneCards database. The “drug component target” network of THSWD was constructed using Cytoscape version 3.8.2 software. The protein interaction was analyzed using STRING platform, the protein–protein interaction (PPI) network was constructed, and the potential protein function modules in the network were mined. Metascape platform was used to analyze “drug component target” and its biological processes and pathways. The clusterProfiler R package was called to perform kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) function enrichment analysis on CGN-related targets regulated by THSWD. Molecular docking verification was performed by AutoDock Vina software. Results: THSWD has 205 target genes and 45 active components, 104 of which are cross with the CGN inflammatory gene. Its main active ingredients, stigmasterol, kaempferol, and sitosterol, have positive relationships with the inflammatory targets of CGN, tumor necrosis factor (TNF), IL-6, AKT1, and MAPK14. THSWD modulates the biological pathway of CGN and mainly acts on TNF-α signal pathway, interleukin-17 signal pathway, etc., whose main functions are response to lipid sugar, heme binding, G protein-coupled amine receptor activity, etc. The results of molecular docking showed that the main active compounds could bind to the core targets and showed good affinity. Conclusion: The molecular mechanism of THSWD in the treatment of CGN from the perspective of network pharmacology are components such as beta-sitosterol, kaempferol, and quercetin and key action targets such as TNF, IL-6, AKT1 protein kinase, and MAPK14 protein kinase play a synergistic role in autoimmune, infection, and inflammatory response-related pathways.

Molecular Mechanism of Xingnao Kaiqiao Pill for Perioperative Neurocognitive Disorder and Its Correlation With Immune and Inflammatory Signaling Pathways Based on Network Pharmacology and Molecular Docking.

To investigate the molecular mechanism of Xingnao Kaiqiao Pill in the treatment of perioperative neurocognitive disorder (PND) from the perspective of network pharmacology and molecular docking technology. Active ingredients of Xingnao Kaiqiao Pill were screened from the traditional Chinese medicine database and analysis platform, and the putative targets were predicted. The GeneCards database was searched to obtain PND-related targets. The genes corresponding to the targets were searched and annotated on the UniProt database. The VennDiagram package in R was employed to obtain common target genes. The overlap genes were introduced into STRING to obtain a protein-protein interaction (PPI) network; thus, key targets were screened. The target relationship network of “Xingnao Kaiqiao Pill–traditional Chinese medicine–compound–common target” was constructed by Cytoscape software. Using R language package Bioconductor, Gene Ontology (GO) and pathway enrichment analysis (Kyoto Encyclopedia of Genes and Genomes Pathway, KEGG Pathway) were performed on the common target genes. A total of 45 active ingredients of Xingnao Kaiqiao Pill were screened, with 182 potential targets, and 1,579 PND-related targets were retrieved from the GeneCards databases (Score ≥ 1). Using VennDiagram, 132 overlap genes were gotten. Xingnao Kaiqiao Pill mainly acted on targets, such as MAPK and JUN. GO enrichment analysis displayed G protein-coupled amine receptor activity, nuclear receptor activity, ligand-activated transcription factor activity, G protein-coupled neurotransmitter receptor activity, steroid hormone receptor activity, and cytokine receptor activity. KEGG enrichment analysis exhibited 157 signaling pathways. The regulation of interleukin 17, tumor necrosis factor, hypoxia-inducible factor-1, and MAPK signaling pathways affected central nervous system (CNS) inflammatory response, cellular immunity, tumor-related signaling pathways, protected neurons, and inhibited PND. The active ingredients of Xingnao Kaiqiao Pill adjust interleukin 17, tumor necrosis factor, hypoxia-inducible factor-1, and MAPK signaling pathways by acting on cell targets, such as JUN, MAPK, AKT1, etc., and finally exert a therapeutic effect on PND.