Background: Cordycepin (Cor), one of the major bioactive components of the traditional
Chinese medicine Cordyceps militaris, has been used in clinical practice for several years. However,
its neuroprotective effect remains unknown.
Aims: The purpose of the study was to evaluate the neuroprotective effects of Cor using a rotenoneinduced
Parkinson’s Disease (PD) rat model and to delineate the possible associated molecular mechanisms.
Methods: In vivo, behavioural tests were performed based on the 10-point scale and grid tests. Levels
of dopamine and its metabolites in the striatum and the numbers of TH-positive neurons in the Substantia
Nigra pars compacta (SNpc) were investigated by high-performance liquid chromatography
with electrochemical detection and immunohistochemical staining, respectively. In vitro, cell apoptosis
rates and Mitochondrial Membrane Potential (MMP) were analysed by flow cytometry and the
mRNA and protein levels of Bax, Bcl-2, Bcl-xL, Cytochrome c (Cyt-c), and caspase-3 were determined
by quantitative real-time PCR and western blotting.
Results: Showed that Cor significantly improved dyskinesia, increased the numbers of TH-positive
neurons in the SNpc, and maintained levels of dopamine and its metabolites in the striatum in rotenone-
induced PD rats. We also found that apoptosis was suppressed and the loss of MMP was reversed
with Cor treatment. Furthermore, Cor markedly down-regulated the expression of Bax, upregulated
Bcl-2 and Bcl-xL, inhibited the activation of caspase-3, and decreased the release of Cyt-c
from the mitochondria to the cytoplasm, as compared to those in the rotenone-treated group.
Conclusion: Therefore, Cor protected dopamine neurons against rotenone-induced apoptosis by improving
mitochondrial dysfunction in a PD model, demonstrating its therapeutic potential for this disease.