Journal
FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.642900
Keywords
parkinson’ s disease; corynoxine; rotenone; autophagy; α -synuclein; neuroinflammation
Categories
Funding
- Natural Science Foundation of China [31800893, 31771124, 31671054, 31900745]
- Shandong Provincial Natural Science Foundation [ZR2020YQ23, ZR2019BC008]
- Health Medical Research Fund, Food and Health Bureau, Hong Kong SAR [HMRF 17182541, HMRF 17182551]
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Cory from Uncaria rhynchophylla has been shown to exhibit neuroprotective effects in rotenone-induced PD animal models by reducing neuroinflammation and diminishing alpha-synuclein aggregates through various pathways.
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 alpha-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 alpha-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.
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