The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice

Abstract

Management of inflammatory bowel disease (IBD) is a real clinical challenge. Despite intense investigation, the mechanisms of IBD remain substantially unidentified. Some inflammatory conditions, such as matrix metalloproteinases (MMPs) and the nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathways, are reported to contribute to the development and maintenance of IBD. Regulation of their common upstream signaling, that is, reactive oxygen species (ROS), may be important to control the progression of IBD. In the present study, we found that procyanidin, a powerful antioxidation flavonoid, has a significant effect on ROS clearance on THP-1 macrophages after lipopolysaccharide (LPS) or LPS-combined adenosine triphosphate stimulation, thus downregulating MMP9 expression, suppressing NF-κB signaling, and interrupting the formation of the NLRP3 inflammasome. Moreover, our in vivo data showed that procyanidin attenuated Dextran sulfate sodium-induced experimental colitis in a dose-dependent fashion by suppressing the expression of MMP9, NF-κB, and NLRP3 inflammasome signaling in colonic tissues in mice. Overall, our results suggested that targeting ROS could be a potential therapeutic choice for colonic inflammation.

Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction

“…Amelioration of the redox status due to the increase in GPx and SOD activity was also observed in the colon tissues of GSPE-treated rats [120]. A preventive effect of procyanidin B2 was also evidenced in a mouse model of DSS-induced colitis [122]. Administration of procyanidin B2 (10-40 mg kg −1 d −1 ) attenuated the severity of tissue damage in the colon and reduced the levels of matrix metalloproteinase-9 (MMP-9), a marker of macrophage infiltration.…”

Role and mechanism of ROS scavengers in alleviating NLRP3‐mediated inflammation

“…Procyanidin, a member of flavonoids, showed its powerful ability on ROS clearance and suppression of NF‐κB signaling in THP‐1 macrophages after LPS stimulation. Meanwhile, the expression of NF‐κB and NLRP3 was suppressed and the formation of NLRP3 inflammasome was interrupted by procyanidin in a dose‐dependent fashion in a DSS‐induced mice colitis model . Dandelion extract mitigated inflammatory signaling NF‐κB p65 and cyclooxygenase‐2 activity induced by LPS in human colonic epithelial cell line HT‐29 cells via suppressing ROS .…”

“…It is widely accepted that NF‐κB signaling is responsible for initiating NLRP3 inflammasome at transcriptional level . Evidence demonstrates that NLRP3 expression could be enhanced when NF‐κB protein level is elevated . Considering the in‐depth relationship between ROS and NF‐κB signaling pathway , it is reasonably assumed that ROS may regulate the NLRP3 inflammasome priming through NF‐κB signaling pathway.…”

Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

“…As we discussed above, the NLRP3 inflammasome is mainly produced in innate immunity cells, thus triggering the cascade immune and inflammatory reaction through the secretion of two pro-inflammatory cytokines including IL-1β and IL-18. As a result, the NLRP3 inflammasome is highly involved in the onset and development of various kinds of diseases, including cardiovascular diseases (myocardial ischemia/infarction, atherosclerosis, and hypertension), metabolic disorders (obesity, diabetes, and metabolic syndrome), digestive diseases (inflammatory bowel disease), renal diseases and CNS diseases ( Chen et al, 2017 ; Kammoun et al, 2018 ; Martinez et al, 2018 ; Nasoohi et al, 2018 ; Sharma et al, 2018 ; Wu et al, 2018b ; Yuan et al, 2018 ). In addition, it has been demonstrated that the polymorphism of the NLRP3 genes may lead to the occurrence of some congenital disorders in patients and animal models ( Lewis et al, 2011 ; Kuemmerle-Deschner et al, 2017 ; Landmann and Walker, 2017 ).…”