title: Paeoniflorin inhibition of 6-hydroxydopamine-induced apoptosis in PC12 cells via suppressing reactive oxygen species-mediated PKCδ/NF-κB pathway.
abstract: Parkinson's disease (PD) is second only to Alzheimer's disease as the most common devastating human neurodegenerative disorder. Despite intense investigation, no curative therapy is available for PD. Paeoniflorin, a monoterpene glucoside isolated from the Paeonia lactiflora Pall., possesses wide pharmacological effects in the nervous system. This study aims at evaluating the effect of paeoniflorin on 6-hydroxydopamine (6-OHDA)-induced apoptosis and to characterize involved signal transduction pathways in PC12 cells. Our results showed that paeoniflorin suppresses mitochondria-mediated apoptosis of PC12 cells induced by 6-OHDA, and anti-apoptotic effects of paeoniflorin on PC12 cells might mainly result from its antioxidant capability by increasing glutathione (GSH). Moreover, we also found that paeoniflorin can dramatically attenuate the 6-OHDA-induced nuclear factor κB (NF-κB) translocation without affecting phosphorylation of Akt, JNK, p38, and ERK1/2. 6-OHDA-induced protein kinase Cδ (PKCδ) upregulation was blocked by paeoniflorin treatment in PC12 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium or NF-κB inhibitor BAY 11-7082 could partially attenuate 6-OHDA-induced cell death. Together, our results indicate that the inhibition of PC12 cell apoptosis by paeoniflorin might be mediated, at least in part, by inhibiting reactive oxygen species (ROS)/PKCδ/NF-κB signaling pathway. This evidence supports the pharmacological potential of paeoniflorin in the management of neurodegenerative disorders associated with oxidative stress, including PD.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.affiliation: Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang 157011, China.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China. Electronic address: dmx1969@126.com.
authors.forename: M
authors.initials: M
authors.lastname: Dong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D039821:Monoterpenes / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D051745:Protein Kinase C-delta / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D006027:Glycosides
chemical_list: D000975:Antioxidants; D045304:Cytochromes c; D005960:Glucosides; D039821:Monoterpenes; D019255:NADPH Oxidases; D016328:NF-kappa B; D018696:Neuroprotective Agents; D016627:Oxidopamine; D051745:Protein Kinase C-delta; D017382:Reactive Oxygen Species; C015423:peoniflorin; D006027:Glycosides
keywords: Paeonia lactiflora Pall; Parkinson’s disease; apoptosis; oxidative stress