Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from and Structural Revision of Two 3,4-Epoxy Group-Containing Abietanes.

Two new 3,4-epoxy group-containing abietane diterpenoids ( and ), together with five known diterpenoids (-), were isolated from . Their structures were elucidated by spectroscopic data analysis, NMR calculations, and X-ray diffraction experiments. The structures of two known abietane diterpenoids were revised based on NMR calculations and X-ray diffraction data. Notably, compound specifically inhibited RSL3-induced ferroptosis with an EC of 56 nM by antioxidation. Moreover, significantly decreased RSL3-induced lipid and cytosolic ROS accumulation and ferroptosis marker gene mRNA expression. This work reports the most potent natural inhibitor against ferroptosis found so far.