Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats

Abstract

BackgroundRheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).MethodsCelastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.ResultsHere we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.ConclusionsOur results validate celastrol as a promising compound for the treatment of arthritis.

Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats

“…5 Celastrol inhibited angiogenesis-mediated tumor growth and alleviated macrophage-mediated inflammation. 20,40 The results of the present study demonstrated that CNMs suppressed the expression of VEGF and MMP-9 in activated macrophages and corneal tissue, suggesting that CNMs might inhibit CNV by downregulation of the secretion activity of macrophages, which is consistent with the in vitro experimental result.…”

Periploca forrestiiSaponin Ameliorates Murine CFA-Induced Arthritis by Suppressing Cytokine Production

“…Periploca forrestii shows several medicinal prophylactic effects in traditional Chinese folk medicine; because several plant saponins were recently found having therapeutic effects in different models of autoimmune diseases, such as arthritis [28, 29], we suggest that PFS may have clinically beneficial effects on autoimmune diseases by their induction of immunosuppression during chronic administration. Therefore, the present study was conducted to evaluate the anti-inflammatory and antiarthritic activities of PFS based on an experimental model of autoimmune arthritis (AIA model).…”

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

“…In vivo , we observed that celastrol has anti-inflammatory effects both in an early and established phase of arthritis development, suppressing ankle swelling, joint inflammatory cell infiltration and proliferation, and serum IL-6 levels in AIA rats (39, 40). This inhibitory effect in cellular infiltration and proliferation may prevent and treat synovial pannus tissue development characteristic of RA patients and responsible for bone damage.…”

“…Importantly, neither blood biochemical parameters nor tissue histological structures revealed drug-induced toxicity associated with the intraperitoneally administration of 1 mg/kg/day of celastrol for 18 days (40). …”