Antrodia camphorata polysaccharide resists 6‐OHDA‐induced dopaminergic neuronal damage by inhibiting ROS‐NLRP3 activation

INTRODUCTION: Parkinson's disease (PD) is a common degenerative disease of the central nervous system (CNS). The main pathological change is the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNPc), thereby leading to dopamine reduction in nigral striatum. 6‐Hydroxydopamine (6‐OHDA), a neurotoxic substance, mediates apoptosis of dopaminergic neurons and causes Parkinson‐like symptoms in mice. METHODS: Our team previously found that Antrodia camphorata polysaccharide (ACP) exerted a good behavioral improvement effect on the PD mouse model established by 6‐OHDA; however, the mechanism remains unknown. Therefore, in this study, we focused on ROS‐NLRP3 signal to investigate the mechanism of 6‐OHDA‐induced apoptosis of dopaminergic neurons MES23.5 and the protective effects of ACP on dopaminergic neurons. RESULT: 6‐OHDA could further activate the expression of inflammasome NLRP3 by inducing ROS, thereby resulting in apoptosis of MES23.5 cells. ACP could inhibit the expression of ROS‐NLRP3 induced by 6‐OHDA, exerting a protective role in MES23.5 cells. Animal experiments also confirmed that ACP intervention could reduce the activation level of ROS‐NLRP3 in the substantia nigra–striatum and improve the exercise capacity of PD mice. CONCLUSION: Our study validated that 6‐OHDA could induce apoptosis of dopaminergic neurons via ROS‐NLRP3 activation. ACP could inhibit this signal and protect dopaminergic neurons, which might be promising in research of PD therapeutics.