Pinocembrin attenuates 6-OHDA-induced neuronal cell death through Nrf2/ARE pathway in SH-SY5Y cells.
Pinocembrin (PB), the most abundant flavonoid in propolis, has been known to display antioxidant activity. However, the mechanism as how PB can induce antioxidant activity remains elusive. The purpose of the present study was to investigate the potential neuroprotective role of PB and to delineate its mechanism of action against the Parkinson's disease-related neurotoxin 6-hydroxydopamine(6-OHDA)-induced cell death in neuroblastoma SH-SY5Y cells. Results indicate that pretreatment with PB for 4 h significantly reduced the 6-OHDA-induced cell viability loss, apoptotic rate and decreased Bcl-2/Bax ratio. In addition, PB inhibited 6-OHDA-induced oxidative stress as measured by the formation of reactive oxygen species, the level of malondialdehyde, mitochondrial membrane potential, and superoxide dismutase. Moreover, we have revealed the PB treatment resulted in an increase in nuclear factor E2-related factor 2 (Nrf2) protein levels and subsequent activation of antioxidant response element (ARE) pathway genes of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) in SH-SY5Y cells. Treatment of SH-SY5Y cells with Nrf2 small interference RNA abolished PB-induced HO-1 and γ-GCS expression and its protective effects. Taken together, these findings suggest that PB can protect the SH-SY5Y cells from 6-OHDA-induced oxidative cell death via Nrf2/ARE pathway. Thus, our study indicates that PB has a partial cytoprotective role in dopaminergic cell culture systems.
Department of Internal Neurology in the People's Hospital of Zhangqiu, Zhangqiu, 250200, China.
Xiaohua
X
Jin
Department of Internal Neurology in the People's Hospital of Zhangqiu, Zhangqiu, 250200, China.
Qian
Q
Liu
Department of Internal Neurology in the People's Hospital of Zhangqiu, Zhangqiu, 250200, China.
Lili
L
Jia
Department of Internal Neurology in the People's Hospital of Zhangqiu, Zhangqiu, 250200, China.
Meng
M
Li
Department of Internal Neurology in the People's Hospital of Zhangqiu, Zhangqiu, 250200, China. 358342097@qq.com.
Xuan
X
Wang
D061745:Antioxidant Response Elements / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016627:Oxidopamine; C016063:pinocembrin