title: Paeonol prevents excitotoxicity in rat pheochromocytoma PC12 cells via downregulation of ERK activation and inhibition of apoptosis.
abstract: Paeonol, an active component of Moutan Cortex, has been recognized as a potential neuroprotective drug. In the present study, an injury model based on glutamate-induced cell death of rat pheochromocytoma cells was used to investigate the neuroprotective potential of paeonol and its mechanism of action. Our findings showed that paeonol dose-dependently prevented glutamate-induced cell death as evidenced by cell viability, lactate dehydrogenase release, and trypan blue exclusion. In addition, flow cytometry of propidium iodide-stained cells revealed that paeonol pretreatment reduced the level of glutamate-induced apoptosis in pheochromocytoma cells. Paeonol was also able to decrease the glutamate-induced injury of mitochondria by normalization of mitochondrial membrane potential and cytochrome c release. The glutamate-induced activity of caspase-3 and p-ERK were dose-dependently reduced by paeonol pretreatments. Taken together, our data suggest that paeonol develops its neuroprotective effect against glutamate neurotoxicity through inhibition of the apoptotic signaling pathway and upregulation of the p-ERK pathway.
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Traditional Chinese Medicine, Hefei, China.
authors.forename: Xuncui
authors.initials: X
authors.lastname: Wang
authors.forename: Guoqi
authors.initials: G
authors.lastname: Zhu
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Li
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000098:Acetophenones; D018696:Neuroprotective Agents; D018698:Glutamic Acid; C013638:paeonol; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; C505410:Casp3 protein, rat; D053148:Caspase 3