Cinnamaldehyde, A Bioactive Compound from the Leaves of Cinnamomum osmophloeum Kaneh, Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the NLRP3 Inflammasome

Abstract

Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the quality of life for affected individuals. The effective management of these conditions remains a persistent challenge. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a complex molecular structure, regulates the production of pro-inflammatory cytokines such as interleukin-1β. Abnormal activation of the NLRP3 inflammasome plays a pivotal role in the development of IBD, making it a compelling target for therapeutic intervention. Our research revealed that cinnamaldehyde (CA), a major bioactive compound found in the leaves of Cinnamomum osmophloeum kaneh, demonstrated a remarkable ability to alleviate colitis induced by dextran sulfate sodium (DSS) in a mouse model. This effect was attributed to CA's ability to downregulate the activation of the NLRP3 inflammasome and reduce the expression of pro-inflammatory mediators in the colon. In the mechanism study, we observed that CA inhibited the NLRP3 inflammasome in macrophages, at least partially, by enhancing the autophagic response, without reducing mitochondrial damage. These findings collectively suggest that CA holds significant potential as a therapeutic agent for enhancing the management of IBD, offering a promising avenue for further research and development.