Tetramethylpyrazine improves oxazolone-induced colitis by inhibiting the NF-κB pathway

Abstract

Tetramethylpyrazine improves oxazolone-induced colitis by inhibiting the NF-κB pathway Abstract Purpose: Tetramethylpyrazine (TMP) is an e ective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. e purpose of this study was to investigate the mechanisms involved in its therapeutic action.Methods: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day a er enema, mice were sacri ced. e in ammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells.Results: Our results showed that TMP improved the colonic in ammatory status as evidenced by histological ndings, as well as SASP. ese e ects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells.Conclusion: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of proin ammatory factor production and oxidative stress.

Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases

“…In vitro assays have demonstrated that tetramethylpyrazine significantly inhibits NF-kB translocation via IkB-a-dependent reduction of pro-inflammatory cytokines, such as TNF-a, IL-6, and IL-8, and the generation of damaging compounds, such as ROS (Scirpo et al, 2015). In addition, the same studies in OXAinduced colitis mice indicated that treatment with Tetramethylpyrazine could improve the outcome of intestinal inflammation via PPARg signaling-mediated inhibition of NF-kB signaling (Lu et al, 2014).…”

Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

“…At intestinal level, for example, under pathological conditions, an enhancement of iNOS expression leads to an over production of nitric oxide (NO). This condition determines a loss of barrier function with epithelial disruption and bacterial translocation, which triggers the inflammation [133,134]. NO has in fact been recognized as involved in the etiology of this kind of mucosal inflammation such as Crohn's disease and ulcerative colitis [135].…”

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease

“…As inhibition of PPAR-γ signaling would lower the beneficial effect of tetramethylpyrazine, it is suggested that the effect of tetramethylpyrazine treatment in colitis is independent of PPAR-γ. In vitro assays also demonstrated that tetramethylpyrazine (40 μg/mL) could significantly inhibit NF-κB translocation, which reduces the production of inflammatory factors TNF-α, IL-6, IL-8, and ROS in LPS treated Caco-2 cells (Lu et al, 2014). These results indicated that tetramethylpyrazine could ameliorate intestinal inflammation by activating the PPAR-γ signaling pathway and inhibiting the NF-κB p65 signaling pathway.…”