Curcumin induces apoptosis and inhibits prostaglandin E2 production in synovial fibroblasts of patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of antiapoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumininduced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E 2 synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

Anti-inflammatory and Anti-oxidant Properties of Curcuma longa (Turmeric) Versus Zingiber officinale (Ginger) Rhizomes in Rat Adjuvant-Induced Arthritis

“…Also, they suppress inflammation by inhibiting the nuclear factor-κB activation, which leads to inhibition of gene expression of proinflammatory cytokines (TNF-α and IL-1β), chemokines (such as MCP-1) and cyclooxygenase (COX)-2 as well as osteoclastogenesis [15,19,36]. COX-2, which converts arachiodonic acid into prostaglandins (PG) such as PGE 2 , is abundantly expressed in the synovial explants of RA by TNF-α and IL-1β [37]. PG greatly potentiate exudates by inducing relaxation of arteriolar smooth muscles and increasing the blood supply to tissues [9].…”

Curcumin inhibits NFκB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells.

“…A number of earlier studies reported the induction of these molecules after curcumin. [38][39][40][41] On the other hand, curcumin suppressed a number of anti-apoptotic (April, Bcl2, Bcl2l, Bcl2l10, Bcl2l2, Cash, MCl1, Mdm2), survival (Birc1e, Birc2, Birc3, Birc5) , DNA repair (Check1, His1) and NFκB activator (Casp8ap2, Bcl10, MyD88, Tank) molecules. Inhibition of these anti-apoptotic/pro-survival molecules and induced apoptosis by curcumin has been reported in varying tumor cell types.…”

Prophylactic role of curcumin against cyclosporine-induced nephrotoxicity: Histological and immunohistological study

“…On the other hand, examination of sections from prophylactic group showed few collagen fibers between the renal tubules. Curcumin significantly attenuated interstitial macrophage influx and renal fibrosis (Kuwabara et al 2006) and might also help to identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in rheumatoid arthritis (Park et al 2007).…”