title: Ellagic acid exerts protective effect in intrastriatal 6-hydroxydopamine rat model of Parkinson's disease: Possible involvement of ERβ/Nrf2/HO-1 signaling.
abstract: Parkinson's disease (PD) is a prevalent movement disorder in the elderly with progressive loss of mesencephalic dopaminergic neurons and incapacitating motor and non-motor complications. Ellagic acid is a natural phenolic compound with potent antioxidant and anti-inflammatory properties. In this study, we investigated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with ellagic acid at a dose of 50mg/kg/day for 1week. Results showed that ellagic acid attenuates apomorphine-induced rotational bias and lowers the latency to initiate and the total time in the narrow beam task and this beneficial effect was partially abrogated following intracerebroventricular microinjection of estrogen receptor β (ERβ) antagonist. Furthermore, ellagic acid reduced striatal malondialdehyde (MDA), reactive oxygen species (ROS), and DNA fragmentation, and improved monoamine oxidase B (MAO-B), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1). Meanwhile, ellagic acid prevented loss of tyrosine hydroxylase (TH)-positive neurons within substantia nigra pars compacta (SNC). These findings indicate neuroprotective potential of ellagic acid in 6-OHDA rat model of PD via amelioration of apoptosis and oxidative stress, suppression of MAO-B, and its favorable influence is partly reliant on ERβ/Nrf2/HO-1 signaling cascade.
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: tmojarad@yahoo.com.
authors.forename: Tourandokht
authors.initials: T
authors.lastname: Baluchnejadmojarad
authors.affiliation: Department of Physiology, School of Medicine, International Campus, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Rabiee
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Zabihnejad
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: mehjour@yahoo.com.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D004610:Ellagic Acid / Q000378:metabolism* / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors; D006419:Heme Oxygenase (Decyclizing); D008315:Malondialdehyde; D023421:Models, Animal; D008995:Monoamine Oxidase; D051267:NF-E2-Related Factor 2; D017072:Neostriatum / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy; D065842:Pars Compacta / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D000975:Antioxidants; D047629:Estrogen Receptor beta; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D004610:Ellagic Acid; D008315:Malondialdehyde; D016627:Oxidopamine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D008995:Monoamine Oxidase
keywords: 6-Hydroxydopamine; Apoptosis; Ellagic acid; Oxidative stress; Parkinson’s disease