Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson’s Disease
Leilei Chen, Yujv Huang, Yu Xing, Jiahong Lu, Wenting Jia, Ju‐Xian Song, Liangfeng Liu, Youcui Wang, Yingyu Huang, Junxia Xie, Min Li
Abstract
Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson’s disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.