A new ferroptosis inhibitor, isolated from Ajuga nipponensis, protects neuronal cells via activating NRF2-antioxidant response elements (AREs) pathway

Ferroptosis is a new form of cell death, and inhibition of ferroptosis is a promising strategy to treat neurological diseases. In this work, sixteen compounds were isolated from Ajuga nipponensis and assayed for anti-ferroptosis activity in HT22 mouse hippocampal neuronal cells. Ajudecunoid C (1, ADC), a new neoclerodane diterpenoid, showed significant inhibitory activity against erastin and RSL3-induced ferroptosis with EC50 values of 4.1 +/- 1.0 and 3.6 +/- 0.3 mu M, respectively. Experimental results demonstrated that ADC effectively prevented ferroptosis through scavenging free radical and activating NRF2-antioxidant response elements (AREs) pathway. This study reveals that ADC, as a new ferroptosis inhibitor, is a promising lead compound for the development of drugs against ferroptosis-related neurological diseases.

Automated summary

The study demonstrated that Ajudecunoid C (ADC), a compound isolated from Ajuga nipponensis, showed inhibitory activity against ferroptosis induced by erastin and RSL3 in HT22 mouse hippocampal neuronal cells. ADC prevented ferroptosis by scavenging free radicals and activating the NRF2-antioxidant response elements (AREs) pathway, making it a promising lead compound for drugs targeting ferroptosis-related neurological diseases.