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Open AccessArticle

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons

1
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
4
Hongcheon Institute of Medicinal Herb, 101 Yeonbongri, Hongcheon 25142, Korea
5
School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea
6
SKKU Advanced Institute of Nanotechnology Sungkyunkwan University, Suwon 16419, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 5832; https://doi.org/10.3390/ijms20235832
Received: 19 October 2019 / Revised: 15 November 2019 / Accepted: 18 November 2019 / Published: 20 November 2019
In our ongoing research to discover natural products with neuroprotective effects, hyperoside (quercetin 3-O-galactoside) was isolated from Acer tegmentosum, which has been used in Korean traditional medicine to treat liver-related disorders. Here, we demonstrated that hyperoside protects cultured dopaminergic neurons from death via reactive oxygen species (ROS)-dependent mechanisms, although other relevant mechanisms of hyperoside activity remain largely uncharacterized. For the first time, we investigated the neuroprotective effects of hyperoside on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in neurons, and the possible underlying mechanisms. Hyperoside significantly ameliorated the loss of neuronal cell viability, lactate dehydrogenase release, excessive ROS accumulation and mitochondrial membrane potential dysfunction associated with 6-OHDA-induced neurotoxicity. Furthermore, hyperoside treatment activated the nuclear erythroid 2-related factor 2 (Nrf2), an upstream molecule of heme oxygenase-1 (HO-1). Hyperoside also induced the expression of HO-1, an antioxidant response gene. Remarkably, we found that the neuroprotective effects of hyperoside were weakened by an Nrf2 small interfering RNA, which blocked the ability of hyperoside to inhibit neuronal death, indicating the vital role of HO-1. Overall, we show that hyperoside, via the induction of Nrf2-dependent HO-1 activation, suppresses neuronal death caused by 6-OHDA-induced oxidative stress. Moreover, Nrf2-dependent HO-1 signaling activation represents a potential preventive and therapeutic target in Parkinson′s disease management. View Full-Text
Keywords: hyperoside; Acer tegmentosum; 6-hydroxydopamine; nuclear factor erythroid 2-related factor 2; heme oxygenase-1; Parkinson′s disease hyperoside; Acer tegmentosum; 6-hydroxydopamine; nuclear factor erythroid 2-related factor 2; heme oxygenase-1; Parkinson′s disease
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MDPI and ACS Style

Kwon, S.-H.; Lee, S.R.; Park, Y.J.; Ra, M.; Lee, Y.; Pang, C.; Kim, K.H. Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons. Int. J. Mol. Sci. 2019, 20, 5832. https://doi.org/10.3390/ijms20235832

AMA Style

Kwon S-H, Lee SR, Park YJ, Ra M, Lee Y, Pang C, Kim KH. Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons. International Journal of Molecular Sciences. 2019; 20(23):5832. https://doi.org/10.3390/ijms20235832

Chicago/Turabian Style

Kwon, Seung-Hwan; Lee, Seoung R.; Park, Yong J.; Ra, Moonjin; Lee, Yongjun; Pang, Changhyun; Kim, Ki H. 2019. "Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons" Int. J. Mol. Sci. 20, no. 23: 5832. https://doi.org/10.3390/ijms20235832

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