Anti-ferroptotic lignan glycosides from Zanthoxylum avicennae : Isolation, structural characterization, and mechanistic evaluation

Introduction

Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, has been implicated in various liver diseases. Small molecules that counteract ferroptosis remain largely restricted to a few synthetic scaffolds, leaving natural products an underexplored source. Zanthoxylum avicennae (Lam.) DC. (Rutaceae) is used against inflammatory and hepatic conditions in Vietnamese traditional medicine. It contains diverse lignans and flavonoids capable of hydrogen-atom-transfer radical scavenging, the mechanism shared by established ferroptosis inhibitors. Its metabolites are therefore potential ferroptosis inhibitors. This study aimed to isolate, structurally characterize, and evaluate the anti-ferroptotic activity of its metabolites.