Mechanism of Modified Danggui Sini Decoction for Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking

Objective. This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. Methods. The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of “drugs-active components-disease targets” was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. Results. Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. Conclusion. Modified Danggui Sini Decoction has the hierarchical network characteristics of “multicomponent, multitarget, multifunction, and multipathway” in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.

Download Full-text

Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9929093 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Kai Niu ◽

Qifang Li ◽

Yuan Liu ◽

Yi Qiao ◽

Bingbing Li ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Active Ingredient ◽

Enrichment Analysis ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Active Ingredients ◽

Scutellariae Radix ◽

Drug Ingredient

This study aims to analyze the targets of the effective active ingredients of Scutellariae radix-Coptidis rhizoma drug pair (SCDP) in ulcerative colitis (UC) by network pharmacology and molecular docking and to explore the associated therapeutic mechanism. The effective active ingredients and targets of SCDP were determined from the TCMSP database, and the drug ingredient-target network was constructed using the Cytoscape software. The disease targets related to UC were searched in GeneCards, DisGeNET, OMIM, and DrugBank databases. Then, the drug ingredient and disease targets were intersected to construct a protein-protein interaction network through the STRING database. The Metascape database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the predicted targets of SCDP for UC. The Autodock software was used for molecular docking between the main active ingredient and the core target to evaluate the binding ability. SCDP has 43 effective active ingredients and 134 intersection targets. Core targets included AKT1, TP53, IL-6, VEGFA, CASP3, JUN, TNF, MYC, EGFR, and PTGS2. GO functional enrichment analysis showed that biological process was mainly associated with a cytokine-mediated signaling pathway, response to an inorganic substance, response to a toxic substance, response to lipopolysaccharide, reactive oxygen species metabolic process, positive regulation of cell death, apoptotic signaling pathway, and response to wounding. KEGG enrichment analysis showed main pathway concentrations were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, bladder cancer, IL-17 signaling pathway, apoptosis, p53 signaling pathway, and PI3K-Akt signaling pathway. The drug active ingredient-core target-key pathway network contains 41 nodes and 108 edges, of which quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol are important active ingredients; PTGS2, CASP3, TP53, IL-6, TNF, and AKT1 are important targets; and the pathways involved in UC treatment include pathways in cancer, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic, apoptosis, IL-17 signaling pathway and herpes simplex infection. The active ingredient has a good binding capacity to the core target. SCDP key active ingredients are mainly quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol, which function mainly by regulating targets, such as PTGS2, CASP3, TP53, IL-6, TNF, and AKT1, and are associated with multiple signaling pathways as pathways in cancer, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathways.

Download Full-text

Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study

Frontiers in Oncology ◽

10.3389/fonc.2021.671382 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lingjian Guo ◽

Haixia Shi ◽

Limin Zhu

Keyword(s):

Gastric Cancer ◽

Molecular Docking ◽

Multidrug Resistance ◽

Signaling Pathway ◽

Akt Signaling ◽

Proteoglycan Synthesis ◽

Network Pharmacology ◽

Signal Pathways ◽

Akt Signaling Pathway ◽

Active Ingredients

Siteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversing the MDR of GC. The chemical composition of STF and genes related to GC were obtained from the TCMNPAS(TCM Network Pharmacology Analysis System, TCMNPAS) Database, and the targets of the active ingredients were predicted using the Swiss Target Prediction Database. The obtained data were mapped to obtain the key active ingredients and core targets of STF in treating GC. The active component-target network and protein interaction network were constructed by Cytoscape and String database, and the key genes and core active ingredients were obtained. The biological functions and related signal pathways corresponding to the key targets were analyzed and then verified via molecular docking. A total of 14 core active ingredients of STF were screened, as well as 20 corresponding targets, which were mainly enriched in cancer pathway, proteoglycan synthesis, PI3K-AKT signaling pathway, and focal adhesion. Molecular docking showed that the core active ingredients related to MDR, namely quercetin and diosgenin, could bind well to the target. In summary, STF may reverse the MDR of GC and exert synergistic effect with chemotherapeutic drugs. It mediates MDR mainly through the action of quercetin and diosgenin on the PI3K/AKT signaling pathway. These findings are the first to demonstrate the molecular mechanism of STF in reversing MDR in GC, thus providing a direction for follow-up basic research.

Download Full-text

Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach

Bioscience Reports ◽

10.1042/bsr20204005 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Bin Liu ◽

Xin Zheng ◽

Jiajun Li ◽

Xiong Li ◽

Ruimei Wu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Cellular Response ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Active Components ◽

Effective Components

Abstract Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches. Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets. Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways. Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.

Download Full-text

Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

Frontiers in Endocrinology ◽

10.3389/fendo.2021.815891 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jinlong Zhao ◽

Fangzheng Lin ◽

Guihong Liang ◽

Yanhong Han ◽

Nanjun Xu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Akt Signaling ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Ppi Network ◽

Active Components ◽

Treatment Of Osteoporosis ◽

Effective Components

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

Download Full-text

Identifying mechanisms of Epimedii Folium against Alzheimer’s disease via a network pharmacology approach Epimedii Folium treats Alzheimer’s disease via PI3K-AKT

European Journal of Inflammation ◽

10.1177/20587392211041435 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110414

Author(s):

Yan Zhao ◽

Guangmei Liu ◽

Yang Yang ◽

Ling Chen ◽

Ying Shang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Signaling Pathway ◽

Target Genes ◽

Kegg Pathway ◽

Target Therapy ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Pathway Gene

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

Download Full-text

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy

Journal of Diabetes Research ◽

10.1155/2021/9941791 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Yixuan Lin ◽

Chuqiao Shen ◽

Fanjing Wang ◽

Zhaohui Fang ◽

Guoming Shen

Keyword(s):

Molecular Docking ◽

Peripheral Neuropathy ◽

Signaling Pathway ◽

Diabetic Peripheral Neuropathy ◽

Kegg Pathway ◽

Network Pharmacology ◽

Chemical Components ◽

Ppi Network ◽

Active Ingredients ◽

Kegg Pathway Analysis

Objective. To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN). Methods. Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the “YQHXTLF Pharmacodynamic Component-DPN Target” regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software. Results. A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets. Conclusion. YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action.

Download Full-text

Based on Network Pharmacology to Explore the Active Ingredients and Molecular Targets of Zuojin Pill for the Treatment of Ulcerative Colitis

10.21203/rs.3.rs-317290/v1 ◽

2021 ◽

Author(s):

Ying Wei ◽

Sichen Ren ◽

Ruilin Wang ◽

Manyi Jing ◽

Honghong Liu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Cellular Response ◽

Mapk Signaling ◽

Akt Signaling ◽

Mapk Signaling Pathway ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Active Components

Abstract Background: Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active component and mechanism of ZJP is still arcane. Objective: This study aims to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC.Methods: Firstly, the components and putative targets of ZJP were collected based on the herbal medicine target database, and a network containing the interaction between the putative targets of ZJP and the potential therapeutic targets of UC was established. Then topological parameters were calculated to identify the key targets in the network and the key targets were imported into David database to perform path enrichment analysis.Results: 7 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, response to drug, cellular response to lipopolysaccharide, MAPK cascade, inflammatory response, immune response, transcription from RNA polymerase II promoter, apoptotic process, regulation of sequence-specific DNA binding transcription factor activity and lipopolysaccharide-mediated signaling pathway. Moreover, PI3K-Akt signaling pathway, MAPK signaling pathway and Toll-like receptor signaling pathway were predicted to participate in the treatment of UC, which directly regulated by 7 active components of ZJP. Quercetin and isorhamnetin have great development value in the treatment of UC. Moupinamide and palmidin A are of great value for exploration because of their safety and innovation.Conclusion: ZJP mainly were directly involved in UC through inflammation and immune regulation by PI3K-Akt signaling pathway and MAPK signaling pathway.

Download Full-text

The Mechanism of Xiaoyao San in the Treatment of Ovarian Cancer by Network Pharmacology and the Effect of Stigmasterol on the PI3K/Akt Pathway

Disease Markers ◽

10.1155/2021/4304507 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Meng Li ◽

Wenqi Zhang ◽

Linqi Yang ◽

Huibing Wang ◽

Yihan Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Molecular Docking ◽

Signaling Pathway ◽

Akt Signaling ◽

Network Pharmacology ◽

Signal Pathways ◽

Akt Signaling Pathway ◽

The Core ◽

And Migration ◽

Proliferation And Migration

Purpose. This study was aimed at exploring the regulatory mechanism of Xiaoyao San (XYS) and its main compound, Stigmasterol, in the biological network and signaling pathway of ovarian cancer (OC) through network pharmacology-based analyses and experimental validation. Methods. The active compounds and targets of XYS were studied by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The GeneCards and OMIM databases were used to screen common targets of XYS in the treatment of OC. Combined with the STRING database and Cytoscape 3.6.0, the core compounds and targets of XYS were obtained. GO and KEGG pathway enrichment analyses of core target genes were carried out by using the Metascape and DAVID databases. Molecular docking has been achieved by using the AutoDock Vina program to discuss the interaction of the core targets and compounds of XYS in the treatment of OC. The effect of Stigmasterol on proliferation and migration were assessed by CCK8 and wound healing assay. Western blot and qRT-PCR were used to analyze the protein and mRNA expressions of PI3K, Akt, and PTEN after treatment of Stigmasterol. Results. A total of 113 common targets of XYS for the treatment of OC were obtained from 975 targets related to OC and 239 targets of XYS’s effect. The main compounds of XYS include Quercetin, Naringenin, Isorhamnetin, and Stigmasterol, which mainly regulate the targets such as TP53, Akt1, and MYC and PI3K/Akt, p53, and cell cycle signal pathways. At the same time, molecular docking showed that Stigmasterol and Akt1 had good docking conformation. Stigmasterol inhibited OC cell proliferation and migration in vitro and reduced the protein and mRNA expressions of the PI3K/Akt signaling pathway. Conclusion. Stigmasterol as the one of the main compounds of XYS suppresses OC cell activities through the PI3K-Akt signaling pathway.

Download Full-text

Retraction: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

RSC Advances ◽

10.1039/d1ra90026a ◽

2021 ◽

Vol 11 (8) ◽

pp. 4441-4441

Author(s):

Laura Fisher

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Akt Signaling ◽

Salvianolic Acid B ◽

Signalling Pathway ◽

Akt Signaling Pathway ◽

Salvianolic Acid ◽

Osteoarthritis Chondrocytes

Retraction of ‘Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signalling pathway in IL-1β-induced osteoarthritis chondrocytes’ by Bin Zhu et al., RSC Adv., 2018, 8, 36422–36429, DOI: 10.1039/C8RA02418A.

Download Full-text

Molecular mechanism underlying the hypolipidemic effect of Shanmei Capsule based on network pharmacology and molecular docking

Technology and Health Care ◽

10.3233/thc-218023 ◽

2021 ◽

Vol 29 ◽

pp. 239-256

Author(s):

Qian Wang ◽

Lijing Du ◽

Jiana Hong ◽

Zhenlin Chen ◽

Huijian Liu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Kegg Pathway ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Signal Pathways ◽

Hypolipidemic Effect ◽

Active Ingredients ◽

Pathway Enrichment

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.

Download Full-text