Wedelolactone: Unveiling the Multifaceted Anti-Inflammatory Potential

Area of Science:

• Pharmacology
• Natural Products
• Drug Discovery

Background:

• Wedelolactone (WED) is a coumarin-derived polyphenol from marigold with traditional medicinal uses.
• Its precise mechanisms of action and safety profile require comprehensive investigation for modern therapeutic applications.

Purpose of the Study:

• To systematically integrate WED's multi-target mechanisms across various diseases, focusing on the AMPK/NF-κB/NLRP3 pathway.
• To clarify the dose-effect relationship and toxicity thresholds of WED.
• To propose strategies for clinical translation, including addressing bioavailability challenges with nanodelivery systems.

Main Methods:

• Systematic literature review and mechanistic pathway analysis.
• Integration of data on dose-response and toxicity studies.
• Exploration of novel therapeutic targets and delivery systems.

Main Results:

• WED modulates key cellular pathways including AMPK/NF-κB/NLRP3, ferroptosis (via GPX4), and the FXR-bile acid axis.
• An effective therapeutic window for WED was identified as 5-100 mg/kg.
• WED demonstrated efficacy in preclinical models of acute lung injury and liver fibrosis.

Conclusions:

• This review provides a unified framework for understanding WED's complex mechanisms of action.
• WED exhibits promising therapeutic potential, supported by defined dosage and safety parameters.
• Nanodelivery systems offer a viable strategy to enhance WED's bioavailability for clinical translation.