Neuroprotective effect of naringin, a flavone glycoside in quinolinic acid-induced neurotoxicity: Possible role of PPAR-γ, Bax/Bcl-2, and caspase-3
Autor: | Gang Wang, Amit D. Kandhare, Anwesha A. Mukherjee-Kandhare, Jian Cui, Subhash L. Bodhankar |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Caspase 3 Pharmacology Toxicology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals RNA Messenger Rats Wistar Naringin Neuroinflammation bcl-2-Associated X Protein Brain Chemistry Behavior Animal Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Chemistry Interleukins Body Weight NF-kappa B Neurotoxicity Organ Size General Medicine Quinolinic Acid medicine.disease Corpus Striatum Rats PPAR gamma Oxidative Stress Neuroprotective Agents 030104 developmental biology Electron Transport Chain Complex Proteins Proto-Oncogene Proteins c-bcl-2 Nitrosative Stress Apoptosis Flavanones Pioglitazone Locomotion 030217 neurology & neurosurgery Food Science medicine.drug Quinolinic acid |
Zdroj: | Food and Chemical Toxicology. 121:95-108 |
ISSN: | 0278-6915 |
Popis: | Huntington's disease (HD) is a complex multifactorial neurodegenerative disorder. Naringin, a flavanone glycoside exhibits potent anti-inflammatory and antiapoptotic effect.To evaluate the effect of naringin in quinolinic acid (QA)-induced neurotoxicity in laboratory rats.Neurotoxicity was induced in male Wistar rats by single intrastriatal injection of QA (300 nmol/4 μl saline) in striatum except non-treated. Rats were administered orally with either vehicle (distilled water (10 mL/kg) or naringin (20, 40 and 80 mg/kg) or pioglitazone (40 mg/kg, p.o.) or its combination for 28 days.Naringin (40 and 80 mg/kg) treatment significantly (p 0.05) attenuated QA-induced alterations in locomotor activity, rearing, grooming, neurological score, footprint analysis, grip strength and a number of slips. QA-induced altered striatal oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde and nitric oxide), neuroinflammatory markers (TNF-α, IL's and NF-kB mRNA) and apoptotic markers (Bax-Bcl-2, Caspase-3, and PPAR-γ mRNA) were significantly attenuated by (p 0.05) by naringin. It also significantly increased (p 0.05) mitochondrial complex (I-IV) activity. TTC scanning also showed that naringin treatment significantly reduced (p 0.05) QA-induced striatal degeneration. It also significantly decreased (p 0.05) OVA-induced elevated striatal apoptosis revealed by flow-cytometric analysis.Naringin exerts its neuroprotective effect against QA-induced neurotoxicity via modulation of oxido-nitrosative stress, neuroinflammatory, apoptotic markers and mitochondrial complex activity. Thus, it may offer a better therapeutic alternative for the management of HD like symptoms. |
Databáze: | OpenAIRE |
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