Cloricromene, a coumarine derivative, protects against collagen‐induced arthritis in Lewis rats

Abstract

1 The aim of the present study was to investigate the e ects of cloricromene, a coumarine derivative, in rats subjected to collagen-induced arthritis. 2 Collagen-induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 ml of the emulsion (containing 100 mg of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. 3 Lewis rats developed an erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA ®rst appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII challenged rats and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. 4 The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg 71 i.p. daily) starting at the onset of arthritis (day 23), delayed the development of the clinical signs at days 24 ± 35 and improved histological status in the knee and paw. 5 Immunohistochemical analysis for iNOS, COX-2, nitrotyrosine and for poly (ADP-ribose) synthetase (PARS) revealed a positive staining in in¯amed joints from collagen-treated rats. The degree of staining for iNOS, COX-2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen-treated rats, which had received cloricromene. 6 Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene-treated rat. 7 This study provides the ®rst evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic in¯ammation and tissue damage associated with collagen-induced arthritis in the rat.

Anti-arthritic Active Fraction of <i>Capparis Spinosa</i> L. Fruits and Its Chemical Constituents

“…22) Blocking these cytokines can thus suppress in‰ammation and ameliorate cartilage destruction. 23) The lyophilized methanolic extract from ‰owering buds of C. spinosa L. was able to counteract the harmful eŠects induced by interleukin1b. 24) Moreover, reports obtained from traditional medical practitioners in Xinjiang of China show that the fruits of C. spinosa L. were used for the treatment of rheumatoid arthritis.…”

Cucurbitacin R Reduces the Inflammation and Bone Damage Associated with Adjuvant Arthritis in Lewis Rats by Suppression of Tumor Necrosis Factor-α in T Lymphocytes and Macrophages

“…TNF-␣, which is involved in inflammation, differentiation, and proliferation of T and B cells, and bone resorption, is the primary agent in the inflammatory process (Rioja et al, 2004), whereas interleukin-1␤ is responsible for the destruction of cartilage and bone (Cuzzocrea et al, 2000). Blocking TNF-␣ suppresses the inflammation and ameliorates cartilage destruction (Cuzzocrea et al, 2000), as this cytokine not only plays a relevant role in leukocyte recruitment to the articulations (Issecutz et al, 1994) but also regulates nitric-oxide synthase-2 and cyclooxygenase-2 expression in the synovial tissue and cartilage of arthritic rats (Amin et al, 1999). This is significant as the metabolites of these enzymes, nitric oxide and prostaglandin E 2 , have an essential function in the development of the inflammatory process (Fahmi, 2004).…”

Anti-Inflammatory Effect of Ebosin on Rat Collagen-Induced Arthritis through Suppressing Production of Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-α

“…Rats were injected intradermally into the right hind metatarsal footpad with 100 fll ofthe emulsion. Seven days later, the rats were injected into the base of the tail again (8). The day of the first immunization was defined as day o.…”

“…Type II CIA in rat has proven to be useful since many of the cellmediated and humoral immunity characteristics in this model are also found in human RA (8). CIA has been extensively used to elucidate the pathogenic mechanisms of RA and to evaluate anti-arthritic drugs, because of its clinical and histological similarities to RA in human with comparable synovitis, bone erosion and pannus formation (9).…”