Abstract: This study aimed to evaluate mechanisms concerning the antioxidant and antiarthritic effects of thymoquinone on collagen-induced rat arthritis (RA) model.Sixty Wistar rats were randomly divided into a normal control group,a model control group,a positive control group,a low-dose,a medium-dose and a high-dose thymoquinone group (n=10).RA model,except for the normal control group,was established by being induced by type II collagen. For 21 continuous days,the three thymoquinone groups were intragastrically administered with low-dose (10 mg/kg),medium-dose (25 mg/kg) and high-dose (50 mg/kg) thymoquinone,the positive control group was intragastrically administered with 8 mg/kg indometacin,and other groups were intragastrically administered with same volume of normal saline.Secondary joint swelling of the rats was determined by a paw volume method.Biochemical indices for oxidative damage,including levels of myeloperoxidase (MPO),malondialdehyde (MDA),superoxide dismutase (SOD) and nitric oxide (NO),were detected.ELISA assay was used to measure the levels of serum inflammatory cytokine interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α) and IL-10.The results showed that 25 mg/kg and 50 mg/kg of thymoquinone remarkably relieved type II collageninduced articular swelling,decreased the levels of MPO,MDA and NO,and increased the SOD activity,being significantly different from those of the model control group (P<0.05).In addition,thymoquinone significantly lowered the contents of IL-1β and TNF-α in serum and promoted the expression of IL-10 (P<0.05).In conclusion,thymoquinone managed to effectively mitigate RA with the mechanism related to the maintained balance between oxidation and antioxidation as well as the suppressed tissue lesions caused by proinflammatory cytokines.

Key words: thymoquinone, arthritis, oxidative stress, inflammatory cytokine