Targeting Oxidative Stress Markers, Xanthine Oxidase, TNFRSF11A and Cathepsin L in Curcumin-Treated Collagen-Induced Arthritis: A Physiological and COSMO-RS Study.

The effectiveness of curcumin in preventing and treating collagen-induced inflammatory arthritis (CIA) in rats and oxidative stress in rats was investigated. We investigated curcumin's curative and preventive effects on paw edema, arthritic size, body weight, and radiologic and histological joint abnormalities. It has been shown that curcumin may dramatically lower the risk of developing arthritis. In addition, the number of white blood cells (WBCs) in the body has dropped, which is a strong indication that curcumin has anti-inflammatory characteristics. A follow-up theoretical investigation of curcumin molecular docking on xanthine oxidase (XO) was carried out after the properties of curcumin were determined using the conductor-like screening model for real solvents (COSMO-RS) theory. Because of the interaction between curcumin and the residues on XO named Ile264, Val259, Asn351, and Leu404, XO may be suppressed by this molecule. Curcumin's anti-inflammatory and antioxidant properties may be responsible for the anti-arthritic effects that have been seen on oxidative stress markers and XO. On the other hand, more research is being conducted to understand its function better in the early stages of rheumatoid arthritis (RA). To determine whether or not curcumin interacts with AR targets, a molecular docking study was conducted using MVD software against TNFRSF11A and cathepsin L.

Thymoquinone strongly inhibits fMLF-induced neutrophil functions and exhibits anti-inflammatory properties in vivo.

Polymorphonuclear neutrophils are key players in host defense against pathogens through the robust production of superoxide anion by the NADPH oxidase and the release of antibacterial proteins from granules. However, inappropriate release of these agents in the extracellular environment induces severe tissue injury, thereby contributing to the physiopathology of acute and chronic inflammatory disorders. Many studies have been carried out to identify molecules capable of inhibiting phagocyte functions, in particular superoxide anion production, for therapeutic purposes. In the present study, we show that thymoquinone (TQ), the major component of the volatile oil from Nigella sativa (black cumin) seeds strongly inhibits fMLF-induced superoxide production and granules exocytosis in neutrophils. The inhibition of superoxide anion was not due to a scavenger effect, as TQ did not inhibit superoxide anion produced by the xanthine/xanthine oxidase system. Interestingly, TQ impaired the phosphorylation on Ser-304 and Ser-328 of p47(PHOX), a cytosolic subunit of the NADPH oxidase. TQ also attenuated specific and azurophilic granule exocytosis in fMLF-stimulated neutrophils as evidenced by decreased cell surface expression of gp91(PHOX) and CD11b, and release of myeloperoxidase. Furthermore, both the PKC and MAPK pathways, which are involved in p47(PHOX) phosphorylation and granules exocytosis, respectively, were inhibited by TQ in fMLF-stimulated neutrophils. Finally, in a model of pleurisy induced by λ-carrageenan in rats, TQ reduced neutrophil accumulation in the pleural space, showing that it not only inhibits PMN functions in vitro, but also exhibits anti-inflammatory properties in vivo. Thus, TQ possesses promising anti-inflammatory therapeutic potential.

Comparison of xanthine oxidase levels in synovial fluid from patients with rheumatoid arthritis and other joint inflammations.

OBJECTIVE: To search whether xanthine oxido-reductase (XOR) present in the synovium is also liberated, to determine its activity in synovial fluid and to establish a possible relationship between XOR levels in rheumatoid arthritis (RA) and non-RA patients. METHODS: This study was carried out in the Laboratory of Immunology, University Ferhat Abbas, Setif, Algeria from 2001-2008. This study is a retrospective controlled study matching cases with RA to non rheumatoid joint inflammations. Synovial fluid (SF) samples were collected with consent of the patients, at Setif University Hospital, from adults suffering from RA (n=36) or only with joint inflammations (n=52). After its detection in SF with indirect enzyme-linked immunosorbent assay (ELISA) and dot-immunobinding, using anti-bovine XOR as first antibodies, XOR was assayed with capture ELISA. RESULTS: Xanthine oxidoreductase is found in all studied SF. Capture ELISA showed levels up to 0.762 and 0.143 mg/mL in SF of RA and other joint inflammations patients, respectively. In most cases, more than 50% of synovial XOR is present as oxidase form. Positive correlation was observed between enzyme level and the disease severity since RA patients had a significantly high enzyme amount compared to patients with other less severe arthritic pathologies. CONCLUSION: These results suggest that the enzyme could well be involved in joint inflammation probably by producing reactive oxygen species.