Chlorogenic Acid Suppresses miR‐155 and Ameliorates Ulcerative Colitis through the NF‐κB/NLRP3 Inflammasome Pathway

SCOPE: The over-activation of the nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of ulcerative colitis (UC). Chlorogenic acid (CGA) exposure is identified as an effective strategy for repressing inflammatory responses. METHODS AND RESULTS: In this study, the NLRP3 inflammasome model with LPS/ATP-induced RAW264.7 cells in vitro and dextran-sulfate-sodium (DSS)-induced colitis in mice are used to evaluate the effect of CGA on NLRP3 inflammasome-related signaling. The results suggest that CGA suppressed the expression of NLRP3 inflammasome-related genes (apoptosis-associated speck-like protein containing CARD (ASC), cysteine-requiring aspartate protease (Caspase)-1 p45, Caspase-1 p20, pro-/cleaved-interleukin (IL)-1β, pro-/cleaved-IL-18), p-nuclear factor kappa B (NF-κB) protein, and miR-155 in mice with colitis. Gain- and loss-of-function studies of miR-155 are performed to elucidate its role in inflammation. Moreover, activation of the NF-κB/NLRP3 inflammasome pathway and miR-155 expression is investigated. CGA exposure in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated RAW264.7 cells leads to a decrease in p-NK-κB and NLRP3 inflammasome-related proteins, which is dependent on the downregulation of miR-155 expression. CONCLUSIONS: These findings indicate that CGA prevented colitis by downregulating miR-155 expression and inactivating the NF-κB/NLRP3 inflammasome pathway in macrophages. The current study has promising therapeutic implications in the treatment of UC.