MODULATORY ROLE OF NIMESULIDE, CAFFEIC ACID AND THEIR COMBINATION AGAINST IMMUNOLOGICALLY INDUCED MOUSE MODEL OF CHRONIC FATIGUE SYNDROME

Chronic Fatigue Syndrome (CFS) is a complex, debilitating illness characterized by persistent and relapsing fatigue that does not improve with rest. This study aimed to explore the neuroprotective effects of nimesulide, and caffeic acid and their combination as an antioxidant in the immunologically induced chronic fatigue-like condition. The CFS was assessed by water-immersion stress test and stress-induced hyperalgesia. Nimesulide (5 and 10 mg/kg), caffeic acid (5 and 10 mg/kg), and their low-dose combination (nimesulide 5mg/kg and caffeic acid 5mg/kg) were administered daily for 21 days. On the 22nd day, the brain of animals was isolated immediately after the behavioral assessments for estimation of oxidative stress markers (SOD, GSH, MDA, and nitrite). The mice challenged with lipopolysaccharide (LPS) used as immunogen (control group) followed by water immersion stress for 21 days showed a significant increase in immobility time and hyperalgesia. The rats also showed decreased levels of antioxidant defense enzymes (SOD, GSH, and MDA), and cortisol levels but markedly increased tumor necrosis factor-alpha (TNF-∝) levels. The daily drugs treated groups showed a significant (p<0.05) reduction in immobility time in stress-induced models and reversed various biochemical alterations as well as TNF-∝ and cortisol levels when compared to the control group. Furthermore, the lower dose combination of nimesulide and caffeic acid significantly (p<0.05) improved behavior performance and attenuated the chronic fatigue-like condition as compared to single drug-treated groups. The result of the present findings strongly demonstrates that the potential antioxidant effect of nimesulide and caffeic acid and its combination has protective effects against immunologic-induced fatigue and could be used in the management of chronic fatigue syndrome.