Morus mesozygia leaf extract ameliorates behavioral deficits, oxidative stress and inflammation in Complete Freund's adjuvant-induced arthritis in rats

Ethnopharmacological relevance: Morus mesozygia Stapf (Moraceae), otherwise referred to as African mulberry, is utilized domestically as a remedy for a variety of inflammatory disorders including rheumatism. Aim: The anti-arthritic effect of the ethylacetate fraction of M. mesozygia leaf extract (EAFMm) was assessed on complete Freund's adjuvant (CFA)-induced arthritis in male Wistar rats. Method: Groups of male Wistar rats were injected with CFA (0.2 mL; 10 mg/mL) in the plantar surface of their right hind paws and treated orally with EAFMm (50 and 100 mg/kg) or its vehicle daily for 28 days. The effect on joint inflammation and mechanical nociception threshold, behavioral deficits (spontaneous motor activity in the open field test and depressive-like symptoms in the forced swim test) was evaluated. The levels and activities of the biomarkers of oxidative-nitrosative stress (reduced glutathione, superoxide dismutase, nitrite, and malondialdehyde) and inflammatory markers [TNF-alpha, IL-6, COX-2, NF kappa B and myeloperoxidase] were also analysed. Results: The EAFMm at the doses of 50 and 100 mg/kg produced a dose dependent reduction in joint inflammation and mechanical hyperalgesia, and as well improved behavioral deficits like spontaneous motor activity and depressive-like behavior. The EAFMm also significantly reduced oxido-nitrosative stress response in the joint and brain tissues. It also decreased TNF-alpha, interleukin-6 levels and myeloperoxidase enzyme activities in joints and brain tissues of rats. Furthermore, EAFMm attenuated the activity of NF kappa B and reduced the cyclooxygenase-2 protein expression level in joint tissues. Conclusion: The ethylacetate fraction of Morus mesozygia leaf extract demonstrated anti-arthritic activity and ameliorated co-morbid depressive-like behavior via inhibition of oxidative stress and inflammation in a rat model of arthritis.