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Planta Med 2017; 83(01/02): 51-56
DOI: 10.1055/s-0042-107471
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice

Yue Qi
1   Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China
,
De-Qiang Dou
2   College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China
,
Hong Jiang
1   Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China
,
Bing-Bing Zhang
2   College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China
,
Wen-Yan Qin
1   Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China
,
Kai Kang
2   College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China
,
Na Zhang
2   College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China
,
Dong Jia
1   Department of Pharmacology, The Second Hospital Affiliated to Liaoning Chinese Medical University, Shenyang, P. R. China
› Author Affiliations
Further Information

Publication History

received 09 December 2015
revised 14 April 2016

accepted 15 April 2016

Publication Date:
25 May 2016 (online)

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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 both in vitro and in vivo in a Parkinsonʼs 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. Amyloid β 1–42 was 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 amyloid β 1–42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β 1–42, 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-3β signalling pathway.

Key words

Alzheimerʼs disease tau - glycogen synthase kinase-3β - phosphatidylinositol-3-kinase - threonineserine protein kinase B
 

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