Targeting inflammasome in digestive diseases: A dual approach of Western and Chinese medicine

Abstract

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a key innate immune complex regulating inflammation and homeostasis. Its aberrant activation drives caspase-1 and interleukin-1β/interleukin-18 maturation, fueling excessive inflammation. Dysregulated NLRP3 signaling is closely linked to digestive diseases including inflammatory bowel disease, acute pancreatitis, and nonalcoholic fatty liver disease, exacerbating barrier dysfunction, tissue injury, and hepatic inflammation. Western medicine strategies target inflammasome assembly, upstream signals, or downstream cytokines; several inhibitors show anti-inflammatory effects in models and early trials, but to date no NLRP3 inhibitor has been approved by the United States Food and Drug Administration for digestive diseases, and face challenges in long-term safety and specificity, with several candidate drugs failing in clinical trials due to hepatotoxicity or poor efficacy. Traditional Chinese medicine (TCM) can affect several targets and pathways. Recent research indicates that TCM components and prescriptions control the activation of NLRP3 via oxidative stress, immune unbalance and inflammatory pathways, providing extra benefits. Therefore, the NLRP3 inflammasome provides an encouraging treatment connection between innate immunity and digestive diseases. Further research should combine Western and TCM mechanisms, increase the clinical evidence and promote translational studies for accurate therapies.