Ziziphus spina-christi fruit extract suppresses oxidative stress and p38 MAPK expression in ulcerative colitis in rats via induction of Nrf2 and HO-1 expression

Abstract

In this study, we aimed to evaluate the anti-inflammatory and protective effects of Ziziphus spina-christi fruit extract (ZFE) against acetic acid (AcOH)-induced colitis in rats. Before a single AcOH instillation, ZFE (100, 200, and 400 mg/kg/day) was administered for 5 days by oral gavage. Pretreatment with ZFE at different doses suppressed the spread of inflammation and inhibited mucosal damage; in addition, it reduced ulcer size and mitigated colitis markers. Administration of ZFE (400 mg/kg) resulted in a greater reduction of inflammatory colonic injury than that after reference drug, mesalazine (MLZ), administration. In addition, ZFE not only histopathologically ameliorated AcOH-induced colitis but also restored the balance between the oxidants and antioxidants. Furthermore, ZFE effectively modulated the mRNA expression of redox-sensitive transcription factors, such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase-1, downregulated the expression of p38 mitogen-activated protein kinase, and upregulated that of vascular endothelial growth factor A and interleukin-1β in AcOH-induced colitis in rats. In conclusion, our results suggested that ZFE could prevent the development of chronic experimental colitis in rats; therefore, it could be considered as an alternative and/or additive therapeutic approach for the management of inflammatory bowel disease.