Chemical constituents and their anti-ferroptosis activities of Ajuga bracteosa

Two new abietane diterpenoids (1 and 2), along with twelve known compounds (3–14), were isolated from the whole plants of Ajuga bracteosa. Their structures were elucidated through a combination of spectroscopic analyses, including NMR and ECD calculations. All isolates were evaluated for their inhibitory effects on RSL3-induced ferroptosis in HT22 cells. Notably, all abietane diterpenoids (1–7) demonstrated moderate to potent anti-ferroptosis activities. Especially, compound 5 exhibited the most potent ferroptosis inhibition with an EC₅₀ of 0.08 μM. Ferroptosis inhibitors hold promising therapeutic potential for neurodegenerative diseases and ischemia/reperfusion injury. This study demonstrates that the abietane-type diterpenoids of A. bracteosa exhibit significant neuroprotective effects against RSL3-induced ferroptosis in HT22 cells.