Wedelolactone: Unveiling the Multifaceted Anti-Inflammatory Potential

BACKGROUND: Wedelolactone (WED) is a polyphenolic compound with a coumarin skeleton isolated from marigold. Despite its wide application in traditional medicine, its mechanisms of action and safety profile require further investigation. SUMMARY: The key contributions of this review lie in: (1) the first systematic integration of WED's multi-target mechanisms across diseases through the AMPK/NF-κB/NLRP3 network; (2) clarification of its dose-effect relationship (effective therapeutic window: 5-100 mg/kg) and toxicity thresholds; (3) proposal of clinical translation strategies, including nanodelivery systems to address bioavailability issues. Recent studies revealed novel mechanisms such as WED's inhibition of ferroptosis via GPX4 and modulation of the FXR-bile acid axis, demonstrating efficacy in acute lung injury and liver fibrosis. KEY MESSAGES: This article provides a comprehensive framework integrating mechanistic insights and translational research for WED's clinical development.