title: Troxerutin exerts neuroprotection in 6-hydroxydopamine lesion rat model of Parkinson's disease: Possible involvement of PI3K/ERβ signaling.
abstract: Parkinson's disease (PD) is a neurodegenerative disease with progressive loss of mesencephalic dopaminergic neurons of the substantia nigra and with multiple incapacitating motor and non-motor symptoms. Troxerutin is a natural bioflavonoid with nephro- and hepato-protective, antioxidant, and anti-inflammatory properties. In this study, we evaluated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with troxerutin at a dose of 150mg/kg/day for 1 week. Results showed that troxerutin mitigates apomorphine-induced motor asymmetry and lowered the latency to initiate and the total time in the narrow beam task and this beneficial effect was lost following central application of estrogen receptor β (ERβ) antagonist or phosphatidylinositol 3-kinase (PI3K) inhibitor. In addition, troxerutin reduced striatal malondialdehyde (MDA) as an index of lipid peroxidation, reactive oxygen species, glial fibrillary acid protein (GFAP) as a marker of astrogliosis, and DNA fragmentation as an apoptotic marker with no significant alteration of catalase activity and nitrite level. Meanwhile, troxerutin was capable to prevent loss of nigral tyrosine hydroxylase (TH)-positive neurons. These findings indicate neuroprotective potential of troxerutin in 6-OHDA rat model of PD through mitigation of apoptosis, astrogliosis, and oxidative stress and part of its effect is dependent on PI3K/ERβ signaling.
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, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nida
authors.initials: N
authors.lastname: Jamali-Raeufy
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.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Rabiee
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; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D047629:Estrogen Receptor beta; D006896:Hydroxyethylrutoside; D018696:Neuroprotective Agents; C005865:troxerutin; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases
keywords: 6-hydroxydopamine; Apoptosis; Oxidative stress; Parkinson’s disease; Troxerutin