Panax quinquefolius ginsenosides for neuroprotection in Parkinson's disease via TNF-α inhibition.

Parkinson's disease (PD) is characterized by resting tremors and gradual loss of dopaminergic (DA) neurons, increasing the socio-economic burden worldwide. This study aimed to investigate the neuroprotective effects of Panax quinquefolius using the MPTP-induced zebrafish PD model. The length and fluorescence intensity of DA neurons were restored to 96.55% and 73.47% of the control values, respectively, under 25 μg/mL total ginsenoside (TG) treatment. The number of blood vessels in the brain was restored to 91.48% of the control values. The swimming distance and speed of zebrafish were restored to 88.21% and 88.19% of the control values, respectively. A total of 15 ginsenosides were identified from TG using liquid chromatography quadrupole time-of-flight mass spectrometry for exploring their actions on PD. The in silico analyses revealed ginsenoside Rg5, pseudoginsenoside F11, and ginsenoside F4 as the key active components, and tumor necrosis factor (TNF), albumin (ALB), TP53, and interleukin (IL)-6 as the important targets with higher correlation degrees. Molecular docking toward TNF-α demonstrated excellent binding affinities with energy values of -7.18 kcal/mol (ginsenoside Rg5), -6.85 kcal/mol (pseudoginsenoside F11), and -7.34 kcal/mol (ginsenoside F4). Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay showed that ginsenosides inhibited MPTP-induced upregulation of TP53 and IL-6 and reversed the downregulation of VDBP, a homologous transport protein of ALB in the zebrafish model. It was speculated that ginsenosides might influence TNF-α protein, which in turn could modulate the downstream TP53, IL-6, and VDBP (ALB) expression, representing an effective mechanism for alleviating PD symptoms.