Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF‐κB pathway

Background Ulcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti‐inflammatory, antiobesity, and other biological activities. However, the therapeutic role and molecular mechanisms of PHI on UC are still insufficiently researched. Methods In this study, dextran sulfate sodium (DSS) and 2.5% 2,4,6‐trinitro‐Benzenesulfonic acid (TNBS)‐induced acute UC were used to investigate the therapeutic effects of PHI. We evaluated the effects of PHI on disease activity index (DAI), body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, enzyme‐linked immunosorbent assay (ELISA), RT‐qPCR, and Western blot analysis. Results Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce DAI and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Mechanistically, PHI may exert anti‐inflammatory effects by downregulating the TLR4/MyD88/NF‐κB pathway and inhibiting the activation of NLRP3 inflammasome. Conclusion In conclusion, PHI possesses significant anti‐inflammatory properties and is expected to be a potential drug for UC treatment. Our study delves into the underlying mechanisms of PHI therapy and highlights the potential for further research in developing PHI‐based treatments for UC. Forsythia suspensa (Thunb.) Vahl extract (PHI) ameliorated both DSS‐ and TNBS‐induced inflammatory bowel disease (IBD) in mice PHI reduced the proportion of inflammatory cells in mesenteric lymph node and peripheral blood mononuclear cells of IBD mice, especially reducing macrophage infiltration into colon PHI inhibited NLRP3 inflammasome activation in IBD mice by downregulating the TLR4/MyD88/NF‐κB signaling pathway, providing a basis for traditional Chinese medicine application in treating this disease.