Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Background. Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear. Materials and Methods. TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF. Results. Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1β, and TNF-α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects. Conclusions. Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways.

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Discussing the Mechanism of Dahuang Huanglian Xiexin Decoction in the Treatment of Type 2 Diabetes Mellitus via Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-531851/v1 ◽

2021 ◽

Author(s):

Xi Cen ◽

Yan Wang ◽

LeiLei Zhang ◽

XiaoXiao Xue ◽

Yan Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Molecular Docking ◽

Target Genes ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Overlapping Genes ◽

Potential Mechanism ◽

Active Components ◽

The Core ◽

Core Genes

Abstract BackgroundType 2 diabetes mellitus (T2DM) is regarded as Pi Dan disease in traditional Chinese medicine (TCM). Dahuang Huanglian Xiexin Decoction (DHXD), a classical TCM formula, has been used for treating Pi Dan disease in clinic, its pharmacological mechanism has not been elucidated. MethodsThis study used network pharmacological analysis and molecular docking approach to explore the mechanism of DHXD on T2DM. Firstly, the compounds in DHXD were obtained from TCMSP and TCMID databases, the potential targets were determined based on TCMSP and UniProt databases. Next, Genecards, Digenet and UniProt databases were used to identify the targets of T2DM. Then, the protein-protein interaction (PPI) network was established with overlapping genes of T2DM and compounds, and the core targets in the network were identified and analyzed. Then, the David database was used for GO and KEGG enrichment analysis. Finally, the target genes were selected and the molecular docking was completed by Autodock software to observe the binding level of active components with target genes.ResultsA total of 397 related components and 128 overlapping genes were identified. After enrichment analysis, it was found that HIF-1, TNF, IL-17 and other signaling pathways, as well as DNA transcription, gene expression, apoptosis and other cellular biological processes had the strongest correlation with the treatment of T2DM by DHXD, and most of them occurred in the extracellular space, plasma membrane and other places, which were related to enzyme binding and protein binding. In addition, 42 core genes of DHXD, such as VEGFA, TP53 and MAPK1, were considered as potential therapeutic targets, indicating the potential mechanism of DHXD on T2DM. Finally, the results of molecular docking showed that HIF-1 pathway had strong correlation with the target genes INSR and GLUT4, quercetin and berberine had the strongest binding power with them respectively.ConclusionThis study summarized the main components of DHXD in the treatment of T2DM, identified the core genes and pathways, and systematically analyzed the interaction of related targets, trying to lay the foundation for clarifying the potential mechanism of DHXD on T2DM, so as to carry out further research in the future.

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NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure

Journal of PHYSIOLOGICAL ANTHROPOLOGY ◽

10.1186/s40101-020-00242-w ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Haiyan Wang ◽

Xue Lin ◽

Xiaoyan Pu

Keyword(s):

Lung Injury ◽

Signaling Pathways ◽

P38 Mapk ◽

Enrichment Analysis ◽

Mapk Signaling ◽

The Body ◽

Inflammatory Factors ◽

Hypoxia Exposure ◽

Tnf Α ◽

Mapk Signaling Pathways

Abstract Background The lung is an important target organ for hypoxia treatment, and hypoxia can induce several diseases in the body. Methods We performed transcriptome sequencing for the lungs of rats exposed to plateau hypoxia at 0 day and 28 days. Sequencing libraries were constructed, and enrichment analysis of the differentially expressed genes (DEGs) was implemented using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, experimental validation was executed by quantitative real-time PCR (qRT-PCR) and western blot. Results The results showed that the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway that was involved in immunity may play a crucial function in lung injury caused by plateau hypoxia. And the expressions of NOD1, NOD2, IL-1β, TNF-α, IL-6, and IL-18 were higher at 28 days of exposure to plateau hypoxia than that at 0 day. Similarly, CARD9, MYD88, p38 MAPK, and NF-κB p65, which are related to the NF-κB and MAPK signaling pathways, also demonstrated increased expression at 28 days exposure to plateau hypoxia than at 0 day. Conclusions Our study suggested that the NFκBp65 and p38 MAPK signaling pathways may be activated in the lungs of rats during plateau hypoxia. Upregulated expression of NFκBp65 and p38 MAPK can promote the transcription of downstream inflammatory factors, thereby aggravating the occurrence and development of lung tissue remodeling.

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Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6421122 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Xiang Yu ◽

Peng Zhang ◽

Kai Tang ◽

Gengyang Shen ◽

Honglin Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Signaling Pathways ◽

Osteoporotic Fracture ◽

Hydrophobic Interactions ◽

Osteoclast Differentiation ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

The Core

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis ( P < 0.05 ), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included ( P < 0.05 ), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3–9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

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Study on the Potential Active Components and Molecular Mechanism of Xiao Huoluo Pills in the Treatment of Cartilage Degeneration of Knee Osteoarthritis based on Bioinformatics Analysis and Molecular Docking Technology

10.21203/rs.3.rs-404023/v2 ◽

2021 ◽

Author(s):

Weijian Chen ◽

Tianye Lin ◽

Qi He ◽

Peng Yang ◽

Gangyu Zhang ◽

...

Keyword(s):

Molecular Docking ◽

Knee Osteoarthritis ◽

Target Genes ◽

Enrichment Analysis ◽

Cartilage Degeneration ◽

Target Protein ◽

Active Components ◽

Binding Ability ◽

R Language ◽

The Core

Abstract Background: Knee osteoarthritis is a common joint degenerative disease that severely affects the quality of life. Modern pharmacological studies have confirmed that Xiao Huoluo Pills (XHLP) has anti-inflammatory, anti-oxidant, and analgesic effects. At present, it has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. Methods: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB>30%, DL≥0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P Value<0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. Results: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 up-regulated genes and 759 down-regulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis.Conclusions: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

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Network pharmacology and molecular docking approaches to investigating the mechanism of action of Zanthoxylum bungeanum in the treatment of oxidative stress-induced diseases

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201117112316 ◽

2020 ◽

Vol 23 ◽

Author(s):

Rong Zhao ◽

Meng-Meng Zhang ◽

Dan Wang ◽

Wei Peng ◽

Qing Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Signaling Pathways ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Zanthoxylum Bungeanum

Background: Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and its related mechanisms are still not systematically reported. Objective: The current study was aimed to explore the main active ingredients and its molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation. Methods: The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology. Results: A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGERAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities. Conclusion: The findings of this study not only indicate the main mechanisms involving in the oxidative stress-induced diseases, but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.

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Integrated Molecular Docking with Network Pharmacology to Reveal the Molecular Mechanism of Simiao Powder in the Treatment of Acute Gouty Arthritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5570968 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Yihua Fan ◽

Wei Liu ◽

Yue Jin ◽

Xu Hou ◽

Xuewu Zhang ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Target Genes ◽

Kegg Pathway ◽

Gouty Arthritis ◽

Enrichment Analysis ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Acute Gouty Arthritis

Background. The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood. Methods. Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with “acute gouty arthritis” and “Arthritis, Gouty” as keywords, respectively. The network of “Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis” was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time. Results. 40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5). Conclusions. Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA.

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Identification of Targets and Active Components of Yiqi SanJie Formula Against Lung Neoplasms Based on Network Pharmacology Analysis and Molecular Docking

Natural Product Communications ◽

10.1177/1934578x21997677 ◽

2021 ◽

Vol 16 (2) ◽

pp. 1934578X2199767

Author(s):

Tian-jiao Zhou ◽

Jun-feng Liu ◽

Ping Wang ◽

An-na Hu ◽

Lin-lin Chen ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Docking ◽

Small Cell Lung Cancer ◽

Signaling Pathways ◽

Lung Neoplasm ◽

Enrichment Analysis ◽

Small Cell ◽

Network Pharmacology ◽

Small Cell Lung ◽

Active Components

Yiqi Sanjie formula (YQSJF) is mainly applied clinically for the treatment of lung neoplasms. The purpose of this study was to explore the pharmacodynamics of the active components of YQSJF and the mechanism of therapeutic effects in the treatment of lung neoplasm diseases based on network pharmacology. The network of component-target, target-pathway, and pathway-disease of YQSJF was constructed by using Cytoscape software. According to the screening result, 37 key components, 57 important targets, and 866 candidate pathways were obtained. The enrichment analysis results indicated that YQSJF might play a therapeutic role in lung cancer by regulating several signaling pathways, such as the PI3K-AKT, non-small cell lung cancer, small cell lung cancer, and apoptosis pathways. There were 53 intersection genes between YQSJF and the lung cancer gene, 52 common genes, and 11 key targets, including CASP8, CASP9, AR, ESR1, PTGS2, NOS3, PGR, TGFB1, PPARG, RELA, and NOS2, screened by using Protein-Protein Interaction (PPI) analysis. These could be the potential therapeutic targets of YQSJF against lung cancer. Enrichment analysis of the intersection gene pathways revealed 10 major functional pathways, including the VEGF, apoptosis, and IL-17 signaling pathways. The molecular docking results showed the potential regulating activity of kaempferol against AR, pelargonidin against PGR, and baicalein against both PTGS2 and AR. In conclusion, combinational network pharmacology analysis results indicated that YQSJF might present its efficacy of alleviating lung neoplasm symptoms through multiple targets in a synergetic way.

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RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways

Oncogene ◽

10.1038/s41388-021-02095-8 ◽

2021 ◽

Author(s):

Jianwei Qu ◽

Yifan Hou ◽

Qingxiao Chen ◽

Jing Chen ◽

Yi Li ◽

...

Keyword(s):

Multiple Myeloma ◽

Signaling Pathways ◽

Critical Role ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Gene Set Enrichment Analysis ◽

Dependent Manner ◽

Growth And Survival ◽

Mapk Signaling Pathways

AbstractN6-methyladenosine (m6A), an internal modification in mRNA, plays a critical role in regulating gene expression. Dysregulation of m6A modifiers promotes oncogenesis through enzymatic functions that disrupt the balance between the deposition and removal of m6A modification on critical transcripts. However, the roles of mRNA m6A in multiple myeloma (MM) are poorly understood. The present study showed that RNA demethylase ALKBH5 was overexpressed in MM and associated with a poor prognosis in MM patients. Knocking down ALKBH5 induced apoptosis and inhibited the growth of MM cells in vitro. Xenograft models and gene set enrichment analysis with patient transcriptome datasets also supported the oncogenic role of ALKBH5 in MM. Mechanistic studies showed that ALKBH5 exerted tumorigenic effects in myeloma in an m6A-dependent manner, and TNF receptor-associated factor 1 (TRAF1) was a critical target of ALKBH5. Specifically, ALKBH5 regulated TRAF1 expression via decreasing m6A abundance in the 3'-untranslated region (3'-UTR) of TRAF1 transcripts and enhancing TRAF1 mRNA stability. As a result, ALKBH5 promoted MM cell growth and survival through TRAF1-mediated activation of NF-κB and MAPK signaling pathways. Collectively, our data demonstrated that ALKBH5 played a critical role in MM tumorigenesis and suggested that ALKBH5 could be a novel therapeutic target in MM.

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Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02552-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weijian Chen ◽

Tianye Lin ◽

Qi He ◽

Peng Yang ◽

Gangyu Zhang ◽

...

Keyword(s):

Molecular Docking ◽

Knee Osteoarthritis ◽

Target Genes ◽

Enrichment Analysis ◽

Cartilage Degeneration ◽

Target Protein ◽

Active Components ◽

Binding Ability ◽

R Language ◽

The Core

Abstract Background Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP’s specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. Methods Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. Results XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis. Conclusions In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

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Mechanism Prediction of Astragalus membranaceus against Cisplatin-Induced Kidney Damage by Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9516726 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Congchao Jia ◽

Xianchao Pan ◽

Binyou Wang ◽

Pengyu Wang ◽

Yiwei Wang ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Kidney Damage ◽

Astragalus Membranaceus ◽

Venn Diagram ◽

Pathway Enrichment Analysis ◽

Active Components ◽

Pathway Enrichment

Background. Cisplatin is a frequently used and effective chemotherapy drug in clinical practice, but severe side effects limit its use, among which nephrotoxicity is considered the most serious and prolonged damage to the body. Astragalus membranaceus (AM) is a well-known herbal medicine, and modern pharmacological studies have confirmed its antioxidant, immunomodulatory, and antiapoptotic effects. Clinical studies have shown that AM and its active components can attenuate cisplatin-induced kidney damage, but the molecular mechanism has not been fully expounded. Materials and Methods. First, the components and targets information of AM were collected from the TCMSP, and the relevant targets of cisplatin-induced kidney damage were accessed from the GeneCards and OMIM databases. Then, the core targets were selected by the Venn diagram and network topology analysis, which was followed by GO and KEGG pathway enrichment analysis. Finally, we construct a component-target-pathway network. Furthermore, molecular docking was carried out to identify the binding activity between active components and key targets. Results. A total of 20 active components and 200 targets of AM and 646 targets related to cisplatin-induced kidney damage were obtained. 91 intersection targets were found between AM and cisplatin-induced kidney damage. Then, 16 core targets were identified, such as MAPK1, TNF-α, and p53. Furthermore, GO and KEGG pathway enrichment analysis suggested that MAPK, Toll-like receptor, and PI3K-Akt signaling pathways may be of significance in the treatment of cisplatin-induced kidney damage by AM. Molecular docking indicated that quercetin and kaempferol had high binding affinities with many core targets. Conclusion. In summary, the active components, key targets, and signaling pathways of AM in the treatment of cisplatin-induced kidney damage were predicted in this study, which contributed to the development and application of AM.

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