(-)-Epicatechin (EC), a dietary flavan-3-ol abundant in tea, cocoa, and certain fruits, has demonstrated promising anti-inflammatory activity. This review summarizes the chemical structure, absorption, distribution, metabolism, and excretion (ADME) characteristics, and molecular mechanisms through which EC modulates inflammation. EC acts both directly—via suppression of factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways—and indirectly through activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-driven antioxidant responses that mitigate inflammatory damage. Importantly, we highlight recent evidence on colonic microbial metabolites of EC, which exhibit diverse and sometimes enhanced bioactivities compared to the parent compound. These low-molecular-weight phenolics participate in immune regulation, redox balance, and intestinal barrier protection, and thereby contribute substantially to the overall anti-inflammatory effects of EC. A core innovation of this review is to highlight that interindividual variability in EC metabolism, largely governed by gut microbiota composition and host enzymatic capacity, generates distinct metabolite profiles. These metabotype-dependent differences provide a mechanistic basis for interindividual variability in the anti-inflammatory efficacy of EC and should be carefully considered when interpreting experimental and clinical findings on EC. Finally, we discuss strategies to enhance EC’s bioavailability, including delivery system optimization and structural modification. This review offers mechanistic and translational insights into EC’s anti-inflammatory potential and highlights the need to integrate microbial metabolism and host factors into future dietary interventions.
Yu et al. (2026) studied this question.