Dataset Information

Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology.

ABSTRACT: Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied that Phellodendron chinense Schneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways.

SUBMITTER: Qian H

PROVIDER: S-EPMC7424379 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology.

Qian Huiqin H Jin Qianqian Q Liu Yichen Y Wang Ning N Chu Yuru Y Liu Bingbing B Liu Yan Y Jiang Wanli W Song Yong Y

Evidence-based complementary and alternative medicine : eCAM 20200804

Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, P ...[more]

PMID: 32831884

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Project description:BackgroundGout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown.ObjectivesTo explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification.MethodsThe ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining.Results48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (-)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1β, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways.ConclusionOur finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.

Project description:Postmenopausal osteoporosis (PMOP) has became 1 of most prevalent bone disorders with aging population. Liuwei Dihuang (LWDH) Pill, a classical kidney-tonifying prescription, is extensively used to treat PMOP in China. The aim of this study is to explore the pharmacological mechanisms of LWDH Pill against PMOP via network pharmacological strategy. The active ingredients of LWDH Pill were screened out from the Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine Databases, and their related target genes were fished in the UniProt database. Simultaneously, the GeneCards and DisGeNET databases were used to identify the target genes of PMOP. Through establishing a protein-protein interaction network, the overlapping genes between LWDH Pill and PMOP were identified to analyze their interactions and the hub target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to predict the underlying biological processes (BP) and signaling pathways, respectively. A total of 64 active ingredients and 653 related target genes were identified in LWDH Pill, and 292 target genes were closely associated with PMOP. After matching the target genes between LWDH Pill and PMOP, 84 overlapping targets were obtained and considered as therapeutically relevant. Through construction of a protein-protein interaction network, we identified 20 hub target genes including IL6, INS, tumor necrosis factor, AKT1, vascular endothelial growth factor A, IGF1, TP53, IL1B, MMP9, JUN, LEP, CTNNB1, EGF, PTGS2, PPARG, CXCL8, IL10, CCL2, FOS and ESR1. Gene Ontology enrichment analysis suggested that LWDH Pill exerted anti-PMOP effects via regulating multiple BP including cell proliferation and apoptosis, oxidative stress, inflammation and angiogenesis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, interleukin-17 (IL-17) pathway and FoxO pathway that might be involved in modulating the above BP. Through network pharmacological approach, we investigated the potential therapeutic mechanism of LWDH Pill against postmenopausal osteoporosis in a systemic perspective. These identified multi-targets and multi-pathways provide promising directions for further revealing more exact mechanisms.

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Project description:PurposeThis study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS).MethodsThe main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of "Chinese herbs-active compounds-targets" for JAKCP was constructed by Cytoscape, and protein-protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of "main active compounds-core targets-pathways" was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot.ResultsA total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1β, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of "T cell activation" demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1β, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro.ConclusionJAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.

Dataset Information

Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology.

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Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology.

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