TCM‐Guided Targeted Therapies Against NLRP3 Inflammasome in NAFLD

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder driven by inflammation, in which the NLRP3 inflammasome plays a central role. Current targeted inhibitors face challenges in patient stratification and long-term safety. METHODS: A narrative literature review was conducted using PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar from database inception to February 2026. Search terms included combinations of "non-alcoholic fatty liver disease", "NAFLD", "NASH", "NLRP3 inflammasome", "traditional Chinese medicine", "TCM", "herbal medicine", "syndrome differentiation", and "precision medicine". Peer-reviewed original articles, systematic reviews, and clinical studies addressing NLRP3 in NAFLD or TCM-based interventions targeting this pathway were prioritized. RESULTS: TCM syndrome patterns (e.g., damp-heat, phlegm-damp) correlate with distinct NLRP3 activation states and inflammatory phenotypes. Herbal compounds such as berberine and curcumin, as well as classical TCM formulae, exert multi-target effects by suppressing NLRP3 inflammasome assembly, enhancing antioxidant defenses, and modulating the gut-liver axis. Based on this evidence, we propose an integrative "TCM Syndrome-NLRP3 Molecular Endotype-Precision Targeted Therapy" model that links specific TCM syndromes to canonical, non-canonical, or sustained NLRP3 activation, thereby providing hypothesis-driven strategies for personalized intervention. DISCUSSION: This integrative framework bridges TCM holistic principles with modern inflammasome biology. It provides a theoretical basis for personalized, biomarker-driven NAFLD therapies, highlighting the synergy between traditional medicine and precision hepatology.