Ukgansan protects dopaminergic neurons from 6-hydroxydopamine neurotoxicity via activation of the nuclear factor (erythroid-derived 2)-like 2 factor signaling pathway. (January 2019)

• Record Type: Journal Article
• Authors: Eo, Hyeyoon; Huh, Eugene; Sim, Yeomoon; Oh, Myung Sook
• Is Part Of: Neurochemistry international. Volume 122(2019)
• Page Start: 208
• Page End: 215
• Publication Date: 2019-01
• Subjects: Ukgansan -- Parkinson's disease -- 6-hydroxydopamine -- Nuclear factor (erythroid-derived 2)-like 2 -- Neuroprotection; Parkinson's disease PD -- substantia nigra pars compacta SNpc -- nuclear factor erythroid-2-related factor 2 Nrf2 -- NAD(P)H:quinone oxidoreductase 1 NQO1 -- heme oxygenase 1 HO-1 -- antioxidant response element ARE -- 6-hydroxydopamine 6-OHDA -- striatum ST -- Roswell Park Memorial Institute medium RPMI -- penicillin-streptomycin P/S -- 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT -- proliferating cell nuclear antigen PCNA -- hydrogen peroxide, 3, 3-diaminobenzidine DAB -- standard error of the mean S.E.M. -- reactive oxygen species ROS -- reactive nitrogen species RNS; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.11.021
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: The sustenance of redox homeostasis in brain is the crucial factor to treat Parkinson's disease (PD). Nuclear factor (erythroid-derived 2)-like 2 factor (Nrf2)-mediated antioxidant response is well known for the main cellular endogenous defense mechanisms against oxidative stress. This study investigated for the first time the effects and possible mechanisms of action of Ukgansan on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in both in vitro and in vivo models of PD. We investigated the protective effect of Ukgansan against 6-OHDA with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In addition, we demonstrated that Ukgansan significantly increased the expression of antioxidant response elements (ARE) and pro-survival protein as Bcl2 and suppressed the expression of pro-apoptotic factors, such as Bax, cytochrome c, and caspase-3 using immunoblotting. For the in vivo study, we used a mouse model of PD involving stereotaxic injection of 6-OHDA into the striatum (ST). Ukgansan alleviated motor dysfunctions induced by 6-OHDA followed by pole, open-field, and rotation tests. Dopaminergic neuronal loss and Nrf2 activation were evaluated by immunohistochemistry in the mouse ST and substantia nigra pars compacta (SNpc) regions. Ukgansan significantly protected dopaminergic neurons from 6-OHDA toxicity in mouse ST and SNpc by activating Nrf2. These results indicate that Ukgansan inhibited 6-OHDA-induced dopaminergic neuronal cell damage via activation of Nrf2 and its related factors in 6-OHDA-induced dopaminergic loss in vitro and in vivo . Thus, Ukgansan might delay the progression of PD via maintenance of redox homeostasis. Graphical abstract: Highlights: UGS promotes the antioxidant defense system via activating Nrf2 against 6-OHDA. Nrf2 activation induces the cell survival signaling pathway in dopaminergic neurons. UGS protects the dopaminergic neuron against 6-OHDA in in vitro and in vivo systems.