Effect of Saffron Extract, Astaxanthin, and Carnosic Acid on the Levels of Matrix Metalloproteinase-9 and on Body Weight Changes in Arthritis Experiments

Abstract AIM The aim of this study was to explore the potential effect of natural compounds and their combination with methotrexate (M) on levels of matrix metalloproteinase-9 (MMP-9) as a key biochemical parameter in rat adjuvant arthritis. Further change of body weight was selected as one of clinical parameters monitored in this animal model. MATERIALS AND METHODS Adjuvant arthritis (AA) was induced in Lewis rats. Methotrexate (M) was administrated twice a week in a dose of 0.3 mg/kg b.w. The saffron extract was administrated daily in two doses: 25 mg/kg b.w. (SF1) and 50 mg/kg b.w. (SF2). Both doses were administrated alone and in combination with M. Astaxanthin was administrated also daily in two doses: 1 mg/kg b.w. (AS1) and 5 mg/kg b.w. (AS2) only as monotherapy. Carnosic acid was administrated daily in one dose: 100 mg/kg (C) in monotherapy and in combination with M. All compounds and M were administrated orally. Plasma samples were collected on the 21st experimental day and used for ELISA determination. The 21st experimental day was used also for the analysis of body weight changes. RESULTS We observed a significant decrease of MMP-9 plasmatic levels in SF1 and SF2 monotherapy in AA animal groups. The decrease in levels of MMP-9 in combined therapy of SF1 and M had higher significance than the effect of M only in AA. The same decreasing effect on the levels of MMP-9 was observed in the combined therapy of C and M. Astaxanthin and saffron extract had a very similar effect on clinical parameters and the change in body weight: both have significantly increased body weight in monotherapy in both doses used. The combined therapy of M and saffron extract doses showed no significant difference from M itself. Carnosic acid did not affect the change of body weight, and the combination of C with M reached the same level as M alone. CONCLUSION Astaxanthin in monotherapy and saffron extract in monotherapy and in combined therapy with M have significantly decreased plasmatic levels of MMP-9 and increased body weight in animals suffering from AA. Lower doses were more efficient for both experiments: astaxanthin and saffron extract. Carnosic acid has no effect in monotherapy in both parameters, but a combination with M has a significant effect with respect to the improvement of cachexia as well as the inhibition of inflammation.