Integrated Multi-Omics Techniques and Network Pharmacology Analysis to Explore the Material Basis and Mechanism of Simiao Pill in the Treatment of Rheumatoid Arthritis
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PROVIDER: S-EPMC10061593 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Project description:Ershiwuwei Lvxue Pill (ELP, མགྲིན་མཚལ་ཉེར་ལྔ།), a traditional Tibetan medicine preparation, has been used hundreds of years for the clinical treatment of rheumatoid arthritis (RA) in the highland region of Tibet, China. Nevertheless, its chemical composition and therapeutic mechanism are unclear. This study aimed to uncover the potentially effective components of ELP and the pharmacological mechanisms against RA by combing UPLC-Q-TOF/MS and network pharmacology. In this study, 96 compounds of ELP were identified or tentatively characterized based on UPLC-Q-TOF/MS analysis. Then, a total of 22 potential bioactive compounds were screened by TCMSP with oral bioavailability and drug-likeness. Preliminarily, 10 crucial targets may be associated with RA through protein-protein interaction network analysis. The functional enrichment analysis indicated that ELP exerted anti-RA effects probably by synergistically regulating many biological pathways, such as PI3K-Akt, Cytokine-cytokine receptor interaction, JAK-STAT, MAPK, TNF, and Toll-like receptor signaling pathway. In addition, good molecular docking scores were highlighted between five promising bioactive compounds (ellagic acid, quercetin, kaempferol, galangin, coptisine) and five core targets (PTGS2, STAT3, VEGFA, MAPK3, TNF). Overall, ELP can exert its anti-RA activity via multicomponent, multitarget, and multichannel mechanisms of action. However, further studies are needed to validate the biological processes and effect pathways of ELP.
| S-EPMC8820630 | biostudies-literature
Project description:ObjectiveHyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets.MethodsSimiao pill-related targets were obtained using Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill.ResultsSimiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds.ConclusionsSimiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF.
| S-EPMC9935928 | biostudies-literature
Project description:Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs participate in the regulations of 24 pathways associated with RA and that 5 herbs in the 7 herbs and 25 compounds in the 5 herbs participate in the regulation of hsa05323 (rheumatoid arthritis). The results indicated that all herbs in LZTB and some compounds in those herbs participate in the treatment of RA; 25 compounds are main active ingredients and hsa05323 (rheumatoid arthritis) is the major pathway in the treatment of RA. We have also found that three pathways (inflammatory mediator regulation of TRP channels, PPAR signaling pathway, and mTOR signaling pathway) might have some effect on the treatment of RA.
| S-EPMC6354157 | biostudies-literature
Project description:To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.
| S-EPMC10796403 | biostudies-literature
Project description:BackgroundWumei Pill (WMP), a famous herbal formula, has been widely used to treat digestive system diseases in clinical practice in China for centuries. We have found a correlation between the indications of WMP and the typical symptoms of pancreatic neoplasms. However, the pharmacological mechanisms of WMP still remain unknown.MethodsIn the present work, we used a network pharmacological method to predict its underlying complex mechanism of treating pancreatic neoplasms. Firstly, we obtained relative compounds of WMP based on TCMSP database, TCM database@Taiwan and TCMID database and collected potential targets of these compounds by target fishing. Then we built the pancreatic neoplasms target database by CTD, TTD, PharmGKB. Based on the matching results between WMP potential targets and pancreatic neoplasms targets, we built a PPI network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, DAVID bioinformatics resources were utilized for the enrichment analysis on GO_BP and KEGG.ResultsA total of 80 active ingredients and 77 targets of WMP were picked out. The results of DAVID enrichment analysis indicated that 58 cellular biological processes (FDR < 0.01) and 17 pathways (FDR < 0.01) of WMP mostly participated in the complex treating effects associated with proliferation, apoptosis, inflammatory response and angiogenesis. Moreover, 17 hub nodes of WMP (PTGS2, BCL2, TP53, IL6, MAPK1, EGFR, EGF, CASP3, JUN, MAPK8, MMP9, VEGFA, TNF, MYC, AKT1, FOS and TGFB1) were recognized as potential targets of treatments, implying the underlying mechanisms of WMP acting on pancreatic neoplasms.ConclusionWMP could alleviate the symptoms of pancreatic neoplasms through the molecular mechanisms predicted by network pharmacology. This study proposes a strategy to elucidate the mechanisms of Traditional Chinese Medicine (TCM) at the level of network pharmacology.
| S-EPMC6611005 | biostudies-literature
Project description:Cinnamomi Ramulus (CR) has been extensively used as a remedy for inflammatory diseases in China. This study adopted an integrative approach of experimental research, phytochemistry, and network pharmacology to investigate its alleviative effects on rheumatoid arthritis (RA) and the underlying potential mechanisms. CR extract (50, 100, and 200 mg/kg) and methotrexate (MTX) significantly ameliorated RA symptoms in the collagen-induced arthritis (CIA) rat model. They also reduced paw volume, arthritis index, proinflammatory cytokines (TNF-α, IL-17A, IL-6, and IL-1β), and oxidative damage. Sixty-three compounds were systematically identified as the basic components of CR. Fifty-five common genes obtained from compounds and GEO databases were employed to construct the protein-protein interaction (PPI) network. Among them, 20 hub genes were identified via the cytoHubba. Enrichment analysis of the common genes indicated that the TNF signaling pathway and IL-17 signaling pathway might be the potential key pathways. Moreover, molecular docking methods confirmed the high affinity between the top 10 bioactive components of CR and the top 10 targets. In addition, in vitro results showed that CR extract (0.2, 0.4, and 0.8 mg/mL) inhibited inflammation and oxidative damage in MH7A cells stimulated by lipopolysaccharide (LPS). In summary, this study adopted multiple approaches to elucidate the protective effect and potential mechanisms of CR on RA, indicating that CR might be a promising herbal candidate for further investigation of RA treatment.
| S-EPMC9499804 | biostudies-literature
Project description:Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay defines health and diseases state of the individual. Rheumatoid arthritis (RA) is a chronic autoimmune disease featured by a systemic immune-inflammatory response, in genetically susceptible individuals exposed to environmental triggers, including diet. In recent years increasing evidences suggested that nutritional factors and gut microbiome have a central role in RA risk and progression. The aim of this review is to summarize the main and most recent applications of 'omics' technologies in human nutrition and in RA research, examining the possible influences of some nutrients and nutritional patterns on RA pathogenesis, following a nutrigenomics approach. The opportunities and challenges of novel 'omics technologies' in the exploration of new avenues in RA and nutritional research to prevent and manage RA will be also discussed.
| S-EPMC7996781 | biostudies-literature
Project description:Lung cancer (LC) has been one of the most prevalent and fatal malignancies in the past 5 years. Yiqi Gubiao pills have a good clinical effect against LC. However, their complex composition limits proper understanding of their pharmacological mechanism. Therefore, the present study aimed to systemically explore the underlying mechanisms of Yiqi Gubiao pills in treatment of LC. The network pharmacology approach was employed to identify the active ingredients and LC targets associated with Yiqi Gubiao pills. Prediction of potential active ingredients and action targets was then conducted through protein-protein interaction (PPI), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In vitro experiments were then performed to further verify the mechanism of action of Yiqi Gubiao pills, revealing that the anti-LC effects were mediated by regulating the expression of IL6, TP53, albumin (ALB), MAPK3 and AKT1. In total, 102 active ingredients and 229 targets of Yiqi Gubiao pills were identified. The PPI network further revealed that AKT1, TP53, ALB, IL6 and MAPK3 were the top five hub genes associated with LC treatment. Targets of the Yiqi Gubiao pills were mainly enriched in the PI3K-Akt and Advanced glycation end products (AGE)-receptors for AGEs (RAGE) signaling pathways. Overall, network pharmacology deciphered the active ingredients and potential targets of the Yiqi Gubiao pills. Yiqi Gubiao pills partially inhibited the progression of LC by regulating the expression of hub genes (AKT1, TP53, ALB, IL6 and MAPK3) through the PI3K-Akt and AGE-RAGE signaling pathways. The findings of the present study may provide a theoretical basis for the clinical application of Yiqi Gubiao pills in LC treatment.
| S-EPMC7933746 | biostudies-literature
Project description:ObjectiveThe aim of this review and meta-analysis was to assess the effects and safety of modified Si-Miao pill (mSMP) in treatment of rheumatoid arthritis.DesignA systematic literature search was carried out in eight databases from their available dates of inception to April 2020. After screening, fifteen randomized, controlled trials (RCTs) comparing the effects and safety of mSMP in combination with western medicine (including disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs)) in treating rheumatoid arthritis patients were included after screening.ResultsIn comparison with DMARDs, or coadministration of DMARDs and NSAIDs, mSMP in combination with western medicine significantly lowered erythrocyte sedimentation rate (mean difference (MD) = -10.61, 95% confidence interval (CI) [-12.19, -9.03]), C-reactive protein (MD = -6.50, 95% CI [-8.43, -4.56]), rheumatoid factors (MD = -17.31, 95% CI [-24.34, -10.27]), swollen joint count (MD = -1.63, 95% CI [-2.29, -0.97]), tender joint count (MD = -1.98, 95% CI [-2.34, -1.62]), and morning stiffness time (MD = -24.37, 95% CI [-29.41, 19.33]) and ameliorated the condition of patients (odds ratio (OR) = 3.69, 95% CI [2.64, 5.14]). Additionally, mSMP in combination with western medicine seemed safer (OR = 0.49, 95% CI [0.30, 0.81]).ConclusionThe results of the meta-analysis study have shown that mSMP in combination with western medicine therapies appears to be more effective and safer than western medicine alone in the treatment of rheumatoid arthritis including reducing inflammatory markers and adverse events and improving symptoms. Howbeit, more high-grade, large-scale RCTs of mSMP in various countries and regions are still needed.
| S-EPMC7261325 | biostudies-literature
Project description:BackgroundDry eye disease (DED) is a multifactorial disease of the ocular surface, which affects the quality of life and work efficiency of affected patients. The traditional Chinese medicine formula Qiju Dihuang Pill (QJDHP) has a good therapeutic effect on DED. However, the pharmacological mechanism is not clear.ObjectiveTo explore the mechanism of QJDHP in the treatment of DED based on network pharmacology.MethodThe active components in QJDHP were screened in Traditional Chinese Medicine Systems Pharmacology (TCMSP), and putative molecular targets of QJDHP were identified using the SwissTargetPrediction database. DED-related targets were screened by GeneCards and OMIM. We established protein-protein interaction (PPI) and core targets and corresponding active compound network by Cytoscape to identify the core targets and main compounds of QJDHP against DED. DAVID database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was used to evaluate the binding activity between key active compounds and core targets.ResultsThe results of network pharmacology showed that 253 targets of QJDHP were related to DED. PPI network analysis showed the 18 core targets. The binding affinity of docking results ranged from -5.7 to -9.3 kcal/mol, indicating a good docking effect. The results of GO enrichment analysis showed that the mechanism of QJDHP in the treatment of DED mainly involved biological processes such as apoptosis, oxidative stress, response to estrogen, angiogenesis, and the regulation of transcription factors. KEGG analysis showed that QJDHP may be regulated by the TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, and estrogen signaling pathway in the treatment of DED.ConclusionIn this study, we demonstrated the multicomponent, multitarget, and multichannel action mechanism of QJDHP in the treatment of DED and provided a foundation for further drug development research.
| S-EPMC9800906 | biostudies-literature