Cordycepin exacerbates cadmium-induced neurotoxicity via promoting endoplasmic reticulum stress-associated apoptosis

Cordycepin (Cor) is a potent bioactive constituent of Cordyceps militaris, which has been used as a daily tonic food and herbal medicine in Asia. Cadmium (Cd) is a widespread neurotoxic environmental contaminant, and it has been detected as a pollutant in Cordyceps militaris. However, the potential effects of Cor on Cd neurotoxicity remains unknown. This study aimed to investigate the effects and possible mechanisms of Cor on neurotoxicity in Cd-induced cell and preclinical models. It was observed that Cor administration aggravated Cd-induced cognitive impairment and neurotoxicity in mice, exerted synergistic growth inhibition, and promoted apoptosis of SHSY5Y cells. These effects were found to be mediated through the activation of endoplasmic reticulum (ER) stress. Overall, our findings suggest that Cor can increase Cd-induced neurotoxicity via promoting ER stressassociated apoptosis. These observations may support the implementation of stricter criterion for the detection of Cd in Cordyceps militaris, to keep the consumers safe.

Automated summary

The study showed that Cor exacerbates Cd-induced cognitive impairment and neurotoxicity in mice, induces synergistic growth inhibition and promotes apoptosis of SHSY5Y cells through the activation of endoplasmic reticulum (ER) stress. This suggests that Cor could enhance Cd-induced neurotoxicity by promoting ER stress-associated apoptosis, leading to potential implications for consumer safety and detection criteria for Cd in Cordyceps militaris.