Ginsenoside Rk1 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease via activating silence information regulator 3-mediated Nrf2/HO-1 signaling pathway.

Abstract

Objectives:Ginsenoside Rk1, a novel ginsenoside isolated from red ginseng, has anti-inflammatory and anti-tumor activities. This study was designed to elucidate therole of RK1 in an in vitro1-methyl-4-phenylpyridinium (MPP+) cell model and an in vivo1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of Parkinson's disease (PD).Methods: The grasping test, pole-climbing test,androtarod testwere performed to measure the effects of RK1 on MPTP-induced motor disorders.The expression of tyrosine hydroxylase (TH) and IBA-1were evaluated by western blotting.CCK-8 and flow cytometry assays were utilized to assess cell viability and apoptosis.Reactive oxygen species (ROS), Lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were detected to analyze the effects of RK1 on oxidative stress. The levels of inflammatory cytokines were evaluated byenzyme-linked immunosorbent assay (ELISA).Results: The results showed that RK1 allayed motor deficitelicited by MPTP in a mouse model.RK1 administration augmented tyrosine hydroxylase (TH) expression in the brain striatum and substantia nigra (SN) of MPTP-treated mice.Moreover, RK1pretreatment promotedviability and suppressed apoptosis in MPP+-induced PC-12cells. Further, RK1 also attenuated MPP+-stimulatedoxidative stressand inflammatory response in PC-12 cells. Besides,RK1 augmented thelevel of SIRT3, and SIRT3 deletion counteracted RK1-induced repression on MPP+-elicited apoptosis, oxidative stress, and inflammatory response in PC-12 cells via modulating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Conclusions: RK1mightexertneuroprotective effectsagainst MPP+/MPTP-induced neurotoxicity via activating SIRT3-mediated Nrf2/HO-1 signaling.RK1 might be a promising candidate against PD.