Protective effect of Plumericin in inflammatory bowel disease: regulation of inflammatory and oxidative stress response in vitro and in vivo

Inflammatory bowel diseases (IBDs) are characterized by chronic relapsing intestinal inflammation. Although IBDs etiology remains unknown, the mechanisms of inflammation and oxidative stress as well as dysbiotic conditions and aberrations in the epithelial barrier are recognized as involved in the pathogenesis of these diseases [1]. Conventional therapy in IBDs uses anti-inflammatory and immunosuppressive corticosteroids, as well as biological drugs, however, the low remission rate and the severe side effects of these therapies are not satisfactory for IBDs pharmacological treatment. Thus, there is a great need for new drugs with anti-inflammatory and anti-oxidant activities. In this study we evaluated the effect of Plumericin, one of the main bioactive components extracted from the bark of Himatanthus sucuuba (Woodson) on intestinal inflammation, both in vitro, on rat intestinal epithelial cells (IEC-6), and in vivo, in an experimental model of DNBS-induced colitis. Our results indicated that Plumericin significantly reduces pro-inflammatory factors with a pivotal role in IBDs, such as tumor necrosis factor-α (TNF-α) levels, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) expression and nitrotyrosine formation. Plumericin was also able to inhibit nuclear factor-kB (NF-kB) activation and to reduce reactive oxygen species (ROS) release. Moreover, Plumericin activates the nuclear factor erythroidderived 2 (Nrf2) anti-oxidant pathway and inhibited inflammasomeactivation in IEC-6. The anti-inflammatory and antioxidant effects observed in vitro, associated with a reduced intestinal macroscopic damage, were confirmed in vivo in DNBS-induced colitis in rat. Plumericin shows anti-inflammatory and antioxidant activities at intestinal level and therefore, could be a promising agent the treatment of IBDs. References [1] Naga K.R. Ghattamanenia S K. Panchal LB. Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease. Pharmacol Res June 2018; 132: 99–107.