1. A series of flavonoids isolated from Indian medicinal plants: kaempferol-3-O-galactoside, hispidulin, nepetin, scutellarein, scutellarein-7-O-glucuronide, hibifolin and morelloflavone were studied for their activity as inhibitors of microsomal lipid peroxidation and scavengers of oxygen free radicals in vitro as well as in a model of xenobiotic toxicity in mouse. 2. All compounds inhibited lipid peroxidation in vitro. The most potent compounds were nepetin (non-enzymic lipid peroxidation) and morelloflavone (enzymic lipid peroxidation) with IC_50's in the micromolar range. Some of the compounds behaved as scavengers of hydroxyl radical in the deoxyribose degradation assay, with a calculated rate constant for kaempferol-3-O-galactoside of 1.55 ± 10¹⁰M⁻¹ s⁻¹. 3. Scutellarein and nepetin were found to be inhibitors of xanthine oxidase activity, whereas morelloflavone acted as a scavenger of superoxide generated by hypoxanthine/ xanthine oxidase. 4. Treatment of mice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactoside after bromobenzene intoxication decreased serum glumate-pyruvate trans-aminase activity, although only the last flavonoid was able to significantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased bromobenzene toxicity.

Objective: CO-releasing molecules (CO-RMs) are a novel class of anti-inflammatory agents. We have examined the possible therapeutic effects of CORM-3 in collagen-induced arthritis (CIA). Methods: Arthritis was induced in DBA-1/J mice by type II collagen. Animals were treated with CORM-3 (5 and 10 mg/kg/day, intraperitoneally) or the inactive compound iCORM-3 (10 mg/kg/day, intraperitoneally) unable to release CO, from days 22 to 31. Production of anti-type II collagen antibodies, cytokines and cartilage olimeric matrix protein (COMP) was evaluated by enzyme-linked immunosorbent assay, and prostaglandin E₂ (PGE₂) by radioimmunoassay. Localisation of cyclooxygenase-2 (COX-2), haem oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and receptor activator of nuclear factor κB ligand (RANKL) was examined by immunohistochemistry. Results: Therapeutic administration of CORM-3 suppressed clinical and histopathological manifestations of disease. The levels of PGE₂, interleukin (IL)1β, IL2, IL6, IL10 and tumour necrosis factor (TNF)α in joint tissues were inhibited by CORM-3. By contrast, CORM-3 augmented IL4. Anti-type II collagen antibodies and COMP levels in serum were reduced by CORM-3. Treatment with CORM-3 decreased cellular infiltration, joint inflammation and destruction, as well as the expression of COX-2, ICAM-1 and RANKL, whereas HO-1 increased. These beneficial effects were due to CO release, as iCORM-3 was ineffective. Conclusion: This study reveals the antiarthritic properties of CORM-3 in the CIA model and supports the notion that CO-RMs could be developed as a novel strategy for the treatment of inflammatory and arthritic conditions.