title: Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.
abstract: Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects bothin vitroandin vivoin a Parkinson's disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloidβ1-42was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloidβ1-42injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloidβ1-42, the mice were sacrificed for biochemical analysis. Arctigenin (10-150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3β. Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3βsignalling pathway.
authors.affiliation: Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China.
authors.forename: De-Qiang
authors.initials: DQ
authors.lastname: Dou
authors.affiliation: Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Qin
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jia
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005663:Furans; D017705:Lignans; C558298:Mapt protein, mouse; D018696:Neuroprotective Agents; D016875:tau Proteins; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C071942:arctigenin