Integrative Pharmacology Powers the Detection of Active Components and Mechanism Underlying Wang Bi Granules in Rheumatoid Arthritis

2021 ◽  
pp. 114468
Author(s):  
Jia Xu ◽  
Hong Chen ◽  
Xiaofang Deng ◽  
Yuanyuan Jiao ◽  
Qiuyan Guo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Components ◽  
Wang Bi

scholarly journals Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Jiao ◽  
Jia Xu ◽  
Hong Chen ◽  
Qiuyan Guo ◽  
Xiaofang Deng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chemical Composition ◽  
Functional Enrichment ◽  
Raw264.7 Cells ◽  
Network Pharmacology ◽  
Regulation System ◽  
Active Components ◽  
Metabolism Regulation ◽  
Tnf Α ◽  
Wang Bi

Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.

scholarly journals Simultaneous Determination of 5 Active Components of Periploca forrestii Schltr Extract in Rat Plasma by UPLC-MS and Its Application to Pharmacokinetic Studies in Normal and Adjuvant-Induced Arthritis Model Rats

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098143
Author(s):  
Hui Liu ◽  
Hao Chen ◽  
Xiaoli Qin ◽  
Xue Ma ◽  
Zipeng Gong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chlorogenic Acid ◽  
Intravenous Administration ◽  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Active Components ◽  
Arthritis Model ◽  
Adjuvant Induced Arthritis ◽  
Neochlorogenic Acid

Periploca forrestii Schltr ( P. forrestii) is a herb used in traditional Chinese medicine for its anti-rheumatoid arthritis effect. The aim of this study was to compare the pharmacokinetic properties of the 5 active components of this plant: neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid C, and periplocin between normal rats and adjuvant-induced arthritis model rats. After the intravenous administration (177.78 mg/kg) of P. forrestii extract, samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Compared with normal rats, the area under the curve [(AUC)(0-t), AUC(0-∞)], mean residence time [(MRT)(0-t), MRT(0-∞)] of neochlorogenic acid-treated rats decreased significantly, and drug clearance (CL) and apparent volume of distribution (V) increased significantly; the V of chlorogenic acid-treated rats decreased significantly, and MRT(0-t) significantly increased; the AUC(0-t) and AUC(0-∞) of cryptochlorogenic acid-treated rats decreased significantly, and CL and V increased significantly; the AUC(0-t) and MRT(0-t) of isochlorogenic acid C-treated rats decreased significantly, and V increased significantly; the AUC(0-t) and AUC(0-∞) of periplocin-treated rats increased significantly, and MRT(0-t), MRT(0-∞), CL, and V decreased significantly in model rats. The disease condition of rheumatoid arthritis in rats had a significant effect on the in vivo pharmacokinetics of P. forrestii after the intravenous administration.

scholarly journals Dissecting the Molecular Mechanism of Wang-Bi Capsule in the Treatment of Experimental Rheumatoid Arthritis Based on Synovial Tissue Proteomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Haiyang Shu ◽  
Yingjie Shi ◽  
Li Li ◽  
Ning Zhao ◽  
Cheng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Proteomic Analysis ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Expression Levels ◽  
Matrix Metalloproteinase 3 ◽  
Cxcr4 Signaling ◽  
Wang Bi

Wang-Bi capsule (WB) is a traditional Chinese medicine formula and has been applied for rheumatoid arthritis (RA) treatment for many years. However, its underlying molecular mechanisms still remain unclear. In this study, collagen-induced arthritis (CIA) rats were used to observe the therapeutic effect of WB used at different time points, and the proteomic analysis of synovial tissue was applied to reveal its basic molecular mechanisms. The results demonstrated that WB not only effectively ameliorated the symptoms and synovitis, but also downregulated the serum levels of inflammatory cytokines/chemokines in CIA rats. Furthermore, the proteomic analysis of synovial tissue showed that WB could regulate several signaling pathways associated with inflammation or cell migration, such as “IL-1 signaling,” “IL-8 signaling,” and “CXCR4 signaling.” The expression levels of proteins including matrix metalloproteinase 3 (MMP3), MMP19, lipopolysaccharide-binding protein (LBP), serine/threonine kinase interleukin-1 receptor-associated kinase 4 (IRAK4), and actin-related protein 2/3 complex subunit 5 (ARPC5) in these pathways were downregulated significantly by WB when compared with the model group. In sum, this study indicated that WB had obvious inhibitory effects on synovitis of CIA rats, and the mechanisms of which may be involved in downregulating the expression levels of several key proteins including MMP3, MMP19, LBP, IRAK4, and ARPC5.

Renin and angiotensin-converting enzyme (ACE) as active components of the local synovial renin-angiotensin system in rheumatoid arthritis

2005 ◽  
Vol 25 (4) ◽  
pp. 285-291 ◽  
Author(s):  
Veli Çobankara ◽  
Mehmet Akif Öztürk ◽  
Sedat Kiraz ◽  
Ihsan Ertenli ◽  
Ibrahim C. Haznedaroglu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Active Components ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Combined Cornus Officinalis and Paeonia Lactiflora Pall Therapy Alleviates Rheumatoid Arthritis by Regulating Synovial Apoptosis via AMPK-Mediated Mitochondrial Fission

2021 ◽  
Vol 12 ◽  
Author(s):  
Lichuang Huang ◽  
Shaoqi Hu ◽  
Meiyu Shao ◽  
Xin Wu ◽  
Jida Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Cartilage Destruction ◽  
Paeonia Lactiflora ◽  
Active Components ◽  
Cornus Officinalis ◽  
Medicinal Value ◽  
Underlying Mechanisms

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to cartilage destruction and bone erosion. In-depth exploration of the pathogenesis of RA and the development of effective therapeutic drugs are of important clinical and social value. Herein, we explored the medicinal value of Cornus officinalis Sieb. and Paeonia lactiflora Pall. in RA treatment using a rat model of collagen-induced arthritis (CIA). We compared the therapeutic effect of Cornus officinalis and Paeonia lactiflora with that of their main active compounds, ursolic acid and paeoniflorin, respectively. We demonstrated that the combination of Cornus officinalis and Paeonia lactiflora effectively inhibited the release of factors associated with oxidative stress and inflammation during RA, therein ameliorating the symptoms and suppressing the progression of RA. We further showed that the underlying mechanisms may be related to the regulation of apoptosis in synovial tissues, and we investigated the potential involvement of AMPK-mediated mitochondrial dynamics in the therapeutic action of the two drugs and their active components.

scholarly journals Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

Oncotarget ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 1193-1202 ◽  
Author(s):  
Qing-Chun Huang ◽  
Mao-Jie Wang ◽  
Xiu-Min Chen ◽  
Wan-Lin Yu ◽  
Yong-Liang Chu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Glycyrrhetinic Acid ◽  
Active Components

scholarly journals Validating potent anti-inflammatory and anti-rheumatoid properties of Drynaria quercifolia rhizome methanolic extract through in vitro, in vivo, in silico and GC-MS-based profiling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Debabrata Modak ◽  
Subhashis Paul ◽  
Sourav Sarkar ◽  
Subarna Thakur ◽  
Soumen Bhattacharjee
Keyword(s):  
Rheumatoid Arthritis ◽  
In Silico ◽  
Methanolic Extract ◽  
Paw Edema ◽  
Active Components ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Background The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management. The goal of the present study was to validate the potent anti-inflammatory and anti-rheumatoid properties of the methanolic-extract of its rhizome using in vitro, in vivo and in silico strategies. Methods The plant was collected and the methanolic extract was prepared from its rhizome. Protein denaturation test, hypotonicity and heat-induced haemolysis assays were performed in vitro. The in vivo anti-rheumatoid potential was assessed in Freund’s complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological and histopathological measurements. Moreover, metabolites of methanolic extract were screened by gas chromatography-mass spectrometry (GC-MS) and 3D molecular structures of active components were utilized for in silico docking study using AutoDock. Results In vitro results evinced a significant (p < 0.05) anti-inflammatory activity of the rhizome methanolic extract in a dose-linear response. Further, Drynaria quercifolia rhizome methanolic extract (DME) significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic paw-edema (in millimeter) in the rat rheumatoid arthritis models in both the low (57.71 ± 0.99, p < 0.01) and high dose groups (54.45 ± 1.30, p < 0.001) when compared to arthritic control. Treatment with DME also normalized the haematological (RBC, WBC, platelet counts and hemoglobin contents) and biochemical parameters (total protein, albumin, creatinine and ceruloplasmin) significantly (p < 0.05), which were further supported by histopathological and radiological analyses. Furthermore, GC-MS analysis of DME demonstrated the presence of 47 phytochemical compounds. Compounds like Squalene, Gamma Tocopherol, n-Hexadecanoic acid showed potent inhibition of cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. Conclusion Results from in vivo and in vitro studies indicated that DME possesses a potent anti-inflammatory and anti-arthritic activity. In silico studies delineated the emergent potent inhibitory effects of several bio-active components on the target inflammatory markers (COX-2, TNF-α and IL-6).

scholarly journals Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Angelicae Pubescentis Radix in the treatment of rheumatoid arthritis

2021 ◽  
Author(s):  
yanni yang ◽  
yirixiati aihaiti ◽  
peng xu ◽  
haishi zheng
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Active Components ◽  
Target Proteins ◽  
Go Enrichment ◽  
Go Enrichment Analysis

Abstract Purpose:To explore the potential target proteins underlying the effect of Angelicae Pubescentis Radix(APR) on rheumatoid arthritis (RA) using a network pharmacology and molecular docking approach .Methods:First, the active components and target proteins of APR and RA related disease targets were obtained from the TCMSP, Gene Card,OMIM,DisGeNET and STRING databases. Then the active ingredient target in the RA network diagram was drawn using Cytoscape 3.7.1 software. Protein-protein interaction analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were carried out using the STRING and David databases. The crystal structures of RA related targets were retrieved from the RCSB PDB database. Finally, the potential active compounds and their related targets were validated using molecular docking technology.Results: Five active components of Angelicae Pubescentis Radix(APR) were screened out, including ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone and 80 key targets including MAPK8,EGFR,PTGS2,CASPASE3,MTOR,SRC,KDR,MAPK1,NOS3 and MAPK14, etc were obtained. GO enrichment analysis showed that 222 biological processes, 34 cell components and 72 molecular functions were identified; KEGG analysis showed that the targets of APR in the treatment of RA were significantly enriched in pathways in cancer, the PI3K−Akt signaling pathway, Proteoglycans in cancer, osteoclast differentiation, neuroactive ligand−receptor interaction, tuberculosis,TNF signaling pathway, serotonergic synapse, Rap1 signaling pathway,cAMP signaling pathway. The results of molecular docking showed that ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone had strong affinity for PTGS2, EGFR and MAPK8.Conclusion: APR treats RA through the characteristics of multi-component, multi-target and multi-pathway regulation.

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