Design of a New Line in Treatment of Experimental Rheumatoid Arthritis by Artesunate

Abstract

This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.

SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-κB pathways in RAW 264.7 macrophages

“…It was reported that artemisinin inhibited NF-κB-mediated iNOS expression and NO synthesis [30] . Owing to this property, several artemisinin derivatives were found to be effective for treating experimental arthritis and lupus nephritis in animal models, however, their bioactivity is limited [31][32][33][34] . SM905 is a novel artemisinin derivative with promising immunosuppressive activity in vitro and in vivo [26] , and oral administration of SM905 induced suppression of collagen-induced arthritis in mice [27] .…”

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

“…By the addition of a hemisuccinate group, artesunate is more water-soluble with greater bioavailability and better pharmacological profile (Newton et al 2000). Apart from its effective anti-malarial actions, artesunate has promising anti-inflammatory potential in animal models of rheumatoid arthritis (Mirshafiey et al 2006;Li et al 2013), systemic lupus erythematosus (Jin et al 2009) and bacteria-induced sepsis (Li et al 2010;Jiang et al 2011). Recently, studies have demonstrated broad anti-inflammatory and anti-oxidative properties of artesunate in experimental allergic asthma (Cheng et al 2011;Ho et al 2012).…”

Camellia Sinensis Modulates Telomerase in Collagen-Induced Arthritis

“…The paws and knees were then removed for histopathological assay. Macroscopic scoring system using a scale from 0 to 4 for each paw was used to evaluate arthritis [7]. On day 35, animals were anesthetized and killed.…”

“…After fixation and decalcification of paws and knees, they stained with hematoxylin and eosin for histological examination. Joint damage was assessed as previously described [7]. According to the severity of damage, joint erosion was graded on a scale of 0 -3 for each limb.…”