Neuroprotective effect of Ginsenoside Re against neurotoxin‑induced Parkinson's disease models via induction of Nrf2

Abstract

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.

Optimal NPK Fertilizer Combination Increases Panax ginseng Yield and Quality and Affects Diversity and Structure of Rhizosphere Fungal Communities

“…The main active compounds in ginseng include ginsenosides, polysaccharides, and polypeptides, among others (Ratan et al, 2020 ). Ginsenosides are important saponins, and it is precise because of those compounds that ginseng is highly valued (Qiao et al, 2022 ). The quality of ginseng medicinal materials is closely related to ginsenoside monomer and total ginsenoside contents in rhizomes.…”

Ginsenoside Rg1 and Re alleviates inflammatory responses and oxidative stress of broiler chicks challenged by lipopolysaccharide

“…The results were consistent with previous reports that the antioxidant and hepatoprotective effects of ginsenoside Rg1 are mainly achieved through induction of the Keap1-Nrf2-ARE signaling pathway ( Gao et al, 2017 ). Wang et al also reported that Re protects neurons from oxidative damage at least in part through induction of the Nrf2/HO-1 pathway ( Qiao et al, 2022 ). Therefore, we hypothesized that ginsenosides Rg1 and Re ameliorated LPS-mediated oxidative stress injury in broilers by mediating the Keap1-Nrf2-ARE pathway.…”

Natural Products as Modulators of Nrf2 Signaling Pathway in Neuroprotection

“…Another experiment with Re (5 μM), but in a PD model with rotenone-intoxicated SH-SY5Y cells, evidenced the same action on viability, apoptosis, and activation of Nrf2 and genes governed by it despite using a lower concentration of the compound. Furthermore, it was concluded that Nrf2 activation occurred through Re stimulation of the PI3K/Akt/Nrf2 and p-ERK/Nrf2 pathways [ 85 ]. On the other hand, in vivo assays have been performed with mice with memory deficits caused by chronic restraint stress.…”