title: Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain.
abstract: Dietary flavonoids have been suggested to promote brain health by protecting brain parenchymal cells. Recently, understanding the possible mechanism underlying neuroprotective efficacy of flavonoids is of great interest. Given that fisetin exerts neuroprotection, we have examined the mechanisms underlying fisetin in regulating Aβ aggregation and neuronal apoptosis induced by aluminium chloride (AlCl3) administration in vivo. Male Swiss albino mice were induced orally with AlCl3 (200 mg/kg. b.wt./day/8 weeks). Fisetin (15 mg/Kg. b.wt. orally) was administered for 4 weeks before AlCl3-induction and administered simultaneously for 8 weeks during AlCl3-induction. We found aggregation of Amyloid beta (Aβ 40-42), elevated expressions of Apoptosis stimulating kinase (ASK-1), p-JNK (c-Jun N-terminal Kinase), p53, cytochrome c, caspases-9 and 3, with altered Bax/Bcl-2 ratio in favour of apoptosis in cortex and hippocampus of AlCl3-administered mice. Furthermore, TUNEL and fluoro-jade C staining demonstrate neurodegeneration in cortex and hippocampus. Notably, treatment with fisetin significantly (P<0.05) reduced Aβ aggregation, ASK-1, p-JNK, p53, cytochrome c, caspase-9 and 3 protein expressions and modulated Bax/Bcl-2 ratio. TUNEL-positive and fluoro-jade C stained cells were also significantly reduced upon fisetin treatment. We have identified the involvement of fisetin in regulating ASK-1 and p-JNK as possible mediator of Aβ aggregation and subsequent neuronal apoptosis during AlCl3-induced neurodegeneration. These findings define the possibility that fisetin may slow or prevent neurodegneration and can be utilised as neuroprotective agent against Alzheimer's and Parkinson's disease.
authors.affiliation: Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamilnadu, India.
authors.forename: Dharmalingam
authors.initials: D
authors.lastname: Prakash
authors.affiliation: Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamilnadu, India. Electronic address: sudhandiran@unom.ac.in.
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000284:Administration, Oral; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000009:adverse effects*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D002712:Chlorides / Q000009:adverse effects*; D045304:Cytochromes c / Q000378:metabolism; D004032:Diet; D005419:Flavonoids / Q000737:chemistry*; D044948:Flavonols; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D051379:Mice; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D000682:Amyloid; D016229:Amyloid beta-Peptides; D002712:Chlorides; D005419:Flavonoids; D044948:Flavonols; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C538897:amyloid beta-protein (40-42); D000077410:Aluminum Chloride; D045304:Cytochromes c; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; C017875:fisetin
keywords: Aluminium chloride; Amyloid-β; Apoptosis; DNA damage; Fisetin; Neurodegeneration