title: Effect of Oleracein E, a Neuroprotective Tetrahydroisoquinoline, on Rotenone-Induced Parkinson's Disease Cell and Animal Models.
abstract: Oleracein E (OE), a tetrahydroisoquinoline possessing potent antioxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pretreatment with OE (10 μM, 2 h) decreased lactic acid dehydrogenase (LDH) release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation. In a rotenone-treated (intragastric 30 mg/(kg·d), 56 d) C57BL-6J mouse model, OE (intragastric 15 mg/(kg·d), 56 d) improved motor function, as indicated by an increased moving distance in the spontaneous activity test and sustained time on the rota-rod test. OE also elevated superoxide dismutase (SOD) activity, decreased malonaldehyde content, and reduced ERK1/2 phosphorylation in the midbrain and striatum of mice treated with rotenone. Furthermore, OE preserved tyrosine hydroxylase-positive neurons and maintained the density of dopaminergic (DAergic) fibers in the substantia nigra pars compacta (SNpc). Some of the effects of OE on PD models were similar to those of the positive control selegiline hydrochloride. Our results demonstrated that OE protects DAergic neurons against rotenone toxicity through reducing oxidative stress and down-regulating stress-related molecules. OE is worth exploring further for its neuroprotectant properties in the prevention and treatment of PD.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: School of Basic Medical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Xiuquan
authors.initials: X
authors.lastname: He
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.|Jinan Hongjitang Pharmaceutical Co. Ltd. , Jinan 250100, China.
authors.forename: Cejia
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Tianyun
authors.initials: T
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yue
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Da
authors.initials: D
authors.lastname: Feng
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gong
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007306:Insecticides / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D018709:Statistics, Nonparametric; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000470:Alkaloids; D007306:Insecticides; D018696:Neuroprotective Agents; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C542300:oleracein E; D012402:Rotenone; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase
keywords: ERK phosphorylation; Parkinson’s disease; Tetrahydroisoquinoline; neuroprotectant; oleracein E; oxidative stress