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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01084

Cajaninstilbene Acid Ameliorates Cognitive Impairment Induced by Intrahippocampal Injection of Amyloid-β1-42 Oligomers

Li-Sha Wang1, Xue Tao1, Xin-Min Liu1, Yun-Feng Zhou1, Meng-Di Zhang1, Yong-Hong Liao1, Rui-Le Pan1* and  Qi Chang1*
  • 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, China

Amyloid-β1-42 (Aβ1-42) oligomers play an important role at the early stage of Alzheimer’s disease (AD) and have been a vital target in the development of therapeutic drugs for AD. Cajaninstilbene acid (CSA), a major bioactive stilbene isolated from pigeon pea (Cajanus cajan) leaves, exerted the neuroprotective property in our previous studies. The present study utilized a validated mouse model of early-stage AD induced by bilateral injection of Aβ1-42 oligomers into hippocampal CA1 regions (100 pmol/mouse) to investigate the cognitive enhancing effects of CSA and the underlying mechanism, by a combination of animal behavioral tests, immunohistochemistry, liquid chromatography-tandem mass spectrometry analysis, and Western blot methods. Intragastric administration of CSA (7.5, 15 and 30 mg/kg) attenuated the impairment of learning and memory induced by Aβ1-42 oligomers. CSA stimulated Aβ clearance and prevented microglial activation and astrocyte reactivity in the hippocampus of model mice. It also decreased the high levels of Glu but increased the low levels of GABA. In addition, CSA inhibited excessive expression of GluN2B-containing NMDARs and upregulated the downstream PKA/CREB/BDNF/TrkB signaling pathway. These results suggest that CSA could be a potential therapeutic agent at the early stage of AD.

Keywords: N-methyl-D-aspartate receptor, Glutamate, astrocyte, Microglia, Cognition, Cajaninstilbene acid, Amyloid-β oligomer, Alzheimer’s disease

Received: 10 Jun 2019; Accepted: 26 Aug 2019.

Copyright: © 2019 Wang, Tao, Liu, Zhou, Zhang, Liao, Pan and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Rui-Le Pan, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100193, Beijing Municipality, China, rlpan@implad.ac.cn
Mx. Qi Chang, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100193, Beijing Municipality, China, qchang@implad.ac.cn