APMCG-1: a mountain-cultivated ginseng-derived glycopeptide alleviates cerebral ischemic injury by resisting oxidative stress, ferroptosis and inflammation via the Nrf2 signaling pathway.

BACKGROUND

APMCG-1 is a glycopeptide derived from the mountain-cultivated ginseng C. A. Mey (APMCG-1), and recent studies have demonstrated its neuroprotective effects. Concurrently, ferroptosis plays an indispensable role in the pathogenesis of ischemic stroke. Investigate the neuroprotective effects of APMCG-1 in mitigating cortical brain injury and neurological dysfunction by suppressing oxidative stress, ferroptosis, and inflammation via the Nrf2 pathway.

METHODS

Rats underwent middle cerebral artery occlusion (MCAO) model. APMCG-1 (20 mg/kg and 40 mg/kg, gavage, 14 days). CoCl2 and glucose-free Dulbecco's Modified Eagle Medium induce hypoxia-glucose deprivation/reperfusion (OGD/R) in a PC12-BV2 co-culture model. APMCG-1 (12.5, 25, and 50 μg/mL, 24 h). The study investigated how APMCG-1 modulates oxidative stress, ferroptosis, and inflammation in rat cortical and neuronal cells via the Nrf2 pathway.

RESULTS

APMCG-1 inhibited oxidative stress, ferroptosis, and inflammation, protecting against cortical injury and neurological dysfunction in MCAO rats, as well as safeguarding cells under OGD/R conditions. These effects were abolished upon Nrf2 inhibition by ML385, indicating that APMCG-1's neuroprotective actions might depend on Nrf2 signaling.

CONCLUSION

APMCG-1 could mitigate cerebral ischemia-reperfusion injury by inhibiting ferroptosis through the Nrf2 pathway, exerting antioxidant effects, and suppressing inflammation, thereby establishing a foundation for potential therapeutic strategies.