title: Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway.
abstract: There is increasing evidence that oxidative stress is critically involved in the pathogenesis of Parkinson's disease (PD), suggesting that pharmacological targeting of the antioxidant machinery may have therapeutic value. Naringenin, a natural flavonoid compound, has been reported to possess neuroprotective effect against PD related pathology; however the mechanisms underlying its beneficial effects are poorly defined. Thus, the purpose of the present study was to investigate the potential neuroprotective role of naringenin and to delineate its mechanism of action against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in models of PD both in vitro and in vivo. Naringenin 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 in SH-SY5Y cells and in mice. Exposure of SH-SY5Y cells to naringenin provided protection against 6-OHDA-induced oxidative insults that was dependent on Nrf2, since treatment with Nrf2 siRNA failed to block against 6-OHDA neurotoxicity or induce Nrf2-dependent cytoprotective genes in SH-SY5Y cells. In mice, oral administration of naringenin resulted in significant protection against 6-OHDA-induced nigrostriatal dopaminergic neurodegeneration and oxidative damage. Our results indicate that activation of Nrf2/ARE signaling by naringenin is strongly associated with its neuroprotective effects against 6-OHDA neurotoxicity and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in PD.
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China.
authors: Haiyan
authors: H
authors: Lou
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China.
authors: Xu
authors: X
authors: Jing
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China.
authors: Xinbing
authors: X
authors: Wei
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China.
authors: Huanying
authors: H
authors: Shi
authors: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012, China.
authors: Dongmei
authors: D
authors: Ren
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China. Electronic address: zhangxm@sdu.edu.cn.
authors: Xiumei
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D016627:Oxidopamine; C005273:naringenin
keywords: 6-OHDA; Naringenin; Nrf2; Oxidative stress; Parkinson's disease