Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression.
10.1016/S1875-5364(18)30064-5
- Author:
Wei-Guang YU
1
;
Yong SHEN
2
;
Jian-Zhong WU
3
;
Yan-Bing GAO
3
;
Li-Xing ZHANG
3
Author Information
1. Department of Orthopedics Lesion Spine, Third Hospital of Hebei Medical University, Shjiazhuang 050000, China.
2. Department of Orthopedics Lesion Spine, Third Hospital of Hebei Medical University, Shjiazhuang 050000, China. Electronic address: shenyongdrug@126.com.
3. Department of Orthopedics Lesion 2, Shijiazhuang No.1 Hospital, Shijiazhuang 050000, China.
- Publication Type:Journal Article
- Keywords:
Adjuvant-induced arthritis;
Fibroblast-like synoviocytes;
Invasion;
Madecassoside;
Matrix metalloproteinase-13;
Rheumatoid arthritis
- MeSH:
Animals;
Antirheumatic Agents;
chemistry;
pharmacology;
therapeutic use;
Arthritis, Experimental;
chemically induced;
drug therapy;
pathology;
Cell Movement;
drug effects;
Cell Nucleus;
metabolism;
Cells, Cultured;
Gene Expression Regulation, Enzymologic;
drug effects;
Interleukin-1beta;
pharmacology;
Matrix Metalloproteinase 13;
genetics;
NF-kappa B;
genetics;
metabolism;
Phosphorylation;
drug effects;
Protein Transport;
drug effects;
Rats;
Signal Transduction;
drug effects;
Synoviocytes;
drug effects;
metabolism;
Transcriptional Activation;
drug effects;
Triterpenes;
chemistry;
pharmacology;
therapeutic use
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(5):330-338
- CountryChina
- Language:English
-
Abstract:
Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.
