title: Pycnogenol Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells Through Regulating NF-κB-iNOS Signaling Pathway.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neurons degeneration and oxidative damage may underlie this process. However, there are still no efficient drugs to cure the disease. Pycnogenol (PYC) isolated from the procyanidin-rich French maritime pine (Pinus maritime) bark has shown various antioxidant activities in previous studies. In this study, we explored its effect against rotenone (Rot)-induced neurotoxicity and the underlying mechanisms in PC12 cells. Using Rot-induced cell model of PD, we found that PYC treatment significantly increased cell viability and decreased cell apoptosis in Rot-treated PC12 cells in a dose-dependent manner. Furthermore, data showed that PYC markedly reduced inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling in Rot-treated PC12 cells. Pretreatment with the iNOS-specific inhibitor significantly attenuated Rot-induced neurotoxicity. Moreover, PYC was found to be capable of reducing Rot-induced NF-κB activation. Blocking NF-κB signaling with its inhibitor mimicked the biological effect of PYC on Rot-induced iNOS and NO expression levels, as well as neurotoxicity in PC12 cells, suggesting that the NF-κB-iNOS signaling pathway was likely to participate in the PYC-mediated protective progress. Our results suggest that PYC protects against Rot-induced neurotoxicity in PC12 cells, and the mechanism may be associated with the downregulation of NF-κB-iNOS signaling pathway.
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Chongwang
authors.initials: C
authors.lastname: Chang
authors.affiliation: 2 Department of Neurosurgery, Lanzhou Military Region General Hospital , Lanzhou, People's Republic of China .
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Zhao
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: 1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects; D010936:Plant Extracts; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D012402:Rotenone / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D016328:NF-kappa B; D010936:Plant Extracts; D020011:Protective Agents; D012402:Rotenone; D009569:Nitric Oxide; C024070:pycnogenols; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat