title: Protective effect of puerarin on lead-induced mouse cognitive impairment via altering activities of acetyl cholinesterase, monoamine oxidase and nitric oxide synthase.
abstract: Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The present study aimed to investigate the protective effects of puerarin on neurotoxicity in mice exposed to lead. ICR mice were exposed to lead acetate in the drinking water (500 ppm) with or without puerarin coadministration (100 and 200 mgPU/kg intragastrically once daily) for three months. We found puerarin significantly prevented Pb-induced neurotoxicity in a dose-dependent manner, indicated by behavioral indicators. Puerarin also decreased Pb contents in blood and brain. Puerarin increased activities of acetyl cholinesterase (AChE) and monoamine oxidase (MAO) in brain of Pb-treated mice. Moreover, Pb-induced profound elevation of oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of total antioxidant capacity in brain, were suppressed by treatment with puerarin. Puerarin markedly increased NO production and PKA activity in brain of Pb-treated mice. Western blot analysis showed that puerarin dramatically increased the expression levels of nNOS, eNOS and phosphor-Akt in brains of Pb-treated mice. In conclusion, these results suggested that puerarin can inhibit Pb-induced neurotoxicity, at least in part, by suppressing oxidative stress, reversing the Pb-induced alterations in transmitters and enzymes and modulating the PKA/Akt/NOS signaling pathway.
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, Xuzhou City 221116, Jiangsu Province, PR China. lcm9009@126.com
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Zheng
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Ming
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Sun
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008995:Monoamine Oxidase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D007529:Isoflavones; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D007854:Lead; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D008995:Monoamine Oxidase; D017868:Cyclic AMP-Dependent Protein Kinases; D000110:Acetylcholinesterase; C033607:puerarin