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

Two new 3,4-epoxy group-containing abietane diterpenoids (1 and 2), together with five known diterpenoids (3-7), were isolated from Ajuga decumbens. 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 4 specifically inhibited RSL3-induced ferroptosis with an EC50 of 56 nM by antioxidation. Moreover, 4 significantly decreased RSL3-induced lipid and cytosolic ROS accumulation and ferroptosis marker gene PTGS2 mRNA expression. This work reports the most potent natural inhibitor against ferroptosis found so far.

Automated summary

This study isolated two new abietane diterpenoids containing 3,4-epoxy groups from Ajuga decumbens, and elucidated their structures through spectroscopic analysis and experiments. One of the compounds exhibited strong antioxidation activity and a significant inhibition against ferroptosis.