The aim of the present study was to examine the neuroprotective effects of a panel of active components of ginseng and to explore their molecular mechanisms of action in two rotenone (Rot)-induced models of Parkinson's disease: An in vitro model using the human neuroblastoma cell line SH-SY5Y and an in vivo model using Drosophila . Ginsenoside Re (Re) was identified as the most potent inhibitor of Rot-induced cytotoxicity in SH-SY5Y cells by Cell Counting kit-8 assay and lactate dehydrogenase release assay. Flow cytometry, Hoechst staining, Rhodamine 123 staining, ATP and cytochrome c release revealed that Re rescue of Rot-induced mitochondrial dysfunction and inhibition of the mitochondrial apoptotic pathway. Western blot analysis demonstrated that Re alleviated Rot-induced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant pathway, and these effects were abolished by RNA interference-mediated knockdown of Nrf2. Re enhanced phosphorylation of components of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinase (ERK) pathways, and pharmacological inhibition of these pathways reduced Re-mediated Nrf2 activation and neuroprotection. In the Drosophila model, Immunofluorescence microscopy, reactive oxygen species (ROS), hydrogen peroxide and knockdown analysis revealed that Re reversed Rot-induced motor deficits and dopaminergic neuron loss while concomitantly alleviating Rot-induced oxidative damage. The findings of the present study suggest that Re protects neurons against Rot-induced mitochondrial dysfunction and oxidative damage, at least in part, by inducing Nrf2/heme oxygenase-1 expression and activation of the dual PI3K/AKT and ERK pathways.

Pueraria Lobata Radix ( P. Lobata Radix) is an edible traditional Chinese medicine that contains various active compounds. Proteins from P. Lobata Radix have become the subject of increased interest in recent years. In evaluating the whitening effect on the skin, the present study found that the P. Lobata Radix water-soluble total protein extract (PLP) had the strongest inhibitory effect on tyrosinase activity. In the present study, the anti-melanogenic effect of PLP and the inhibitory effect on B16 melanoma cells were investigated. PLP significantly reduced the tyrosinase activity and melanin content in B16 melanoma cells. Mechanistically, PLP inhibited melanogenesis by decreasing the expression of tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 through downregulation of the microphthalmia-associated transcription factor (MITF) gene, which was mediated by inhibition of p38 mitogen-activated protein kinase signaling. In addition, PLP inhibited cell viability and triggered apoptosis of B16 cells in a dose-dependent manner. Exposure to PLP reduced the mitochondrial membrane potential (MMP) and decreased ATP generation, leading to mitochondria-related apoptosis of B16 melanoma cells. The expression levels of succinate dehydrogenase (SDH) and its two related subunits (SDHA and SDHB) were downregulated significantly by PLP, which may be associated with the regulation of mitochondrial energy metabolism by PLP. These results may explain why MMP collapse and reduced ATP generation were observed in B16 melanoma cells treated with PLP. Finally, the present study demonstrated that the inhibition of melanin synthesis by PLP was correlated with the regulation of antioxidant enzymes to reduce reactive oxygen species levels. These results suggested that PLP inhibits melanogenesis by downregulating the expression of MITF-related melanogenic enzymes and triggering apoptosis through mitochondria-related pathways.