Protective effect of ginsenoside CK against MPTP-induced Parkinson' s disease mouse model by suppressing oxidative stress and inflammation, and modulating the gut microbiota.

Ginsenoside CK (CK) is a metabolite of natural diol ginsenoside in the intestine, which has a unique chemical structure and pharmacological activity. CK has great potential in the treatment of neurologic dysfunction diseases. However, the therapeutic effect and potential mechanism of CK on Parkinson's disease (PD) have not been studied. Accordingly, this study used microbiome analysis to correlate behavioral, physiological and biochemical indices, and combined with WB to elucidate the mechanism of CK's improvement on PD. CK showed significant therapeutic effects on PD mice, which improved behavioral abnormalities such as spatial memory ability and motor coordination in PD mice, increased the activities of T-AOC and GSH-Px, decreased the MDA content, thus alleviating oxidative stress injury, suppressed the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α, and activated the expression of anti-inflammatory factor IL-2, which then exerted against neuroinflammation, inhibited the apoptosis of dopaminergic neurons in the substantia nigra of PD mice, increased the expression of TH, and prevented the aggregation of α-Syn in the substantia nigra. Microbiomics analysis showed that CK treatment could reshape the gut microbiota of PD mice by increasing the abundance of probiotics (Bacteroides anomalies) and decreasing the number of pathogenic bacteria (Actinomycetes). Correlation analysis showed that gut microbiota had potential correlation with behavioral, physiological and biochemical indexes. Western blot results showed that CK inhibited the expression levels of apoptotic proteins Bax, caspase-3, and Bcl-2, which revealed that CK treatment could improve the dysfunction of MPTP-induced PD mice from the molecular level. Collectively, these findings will provide a basis for further development of CK as an anti-PD drug.