ReferenceID 1954

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis

Front Pharmacol

Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to trea

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Reference Id
1954
Evidence Id
18544
Core Evidence Id
18544
Source Reference Id
3921
Herb2 Reference Id
HBREF004718
Subject Paper Key
HBIN027510_32477105
Pubmed Id
32477105
Doi
10.3389/fphar.2020.00515
Paper Title
Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis
Paper Abstract
Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-alpha)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-alpha-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1beta secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-kappaB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-kappaB-NLRP3 axis to alleviate RA symptoms. Chemical compounds studied in this article: Gentiopicroside (PubChem CID: 88708).
Journal
Front Pharmacol
Publish Year
2020
Experiment Subject
rat; human; ra-fls cells; treated cells; tumor necrosis factor alpha (tnf-alpha)-stimulated human ra fibroblast-like synoviocytes
Experiment Type
Animal & Cell Experiment
Phenotype Related
Tumor; Rheumatoid Arthritis; Swelling Of Joints; Synovial Hyperplasia; Arthritis; Gentiopicroside; Autoimmunity
Paper Title Cn
Paper Title En
Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis
Bilingual Status
semi_complete