Honokiol Attenuates the Memory Impairments, Oxidative Stress, Neuroinflammation, and GSK-3β Activation in Vascular Dementia Rats

Article type: Research Article

Authors: Guo, Si^{a; b; 1; *} | Xu, Jing-Jing^{c; d; e; 1} | Wei, Na^{c; d; e} | Han, Jun-Ya^{c; f} | Xue, Rui^g | Xu, Po-Shi^{a; b} | Gao, Chuan-Yu^{h; i; *}

Affiliations: [a] Department of Medical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China | [b] Department of Medical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, People’s Republic of China | [c] Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China | [d] Henan Key Laboratory of Tumor Pathology, Zhengzhou, People’s Republic of China | [e] Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou, People’s Republic of China | [f] Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China | [g] Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China | [h] Department of Cardiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China | [i] Department of Cardiology, Fuwai Central China Cardiovascular Hospital, Zhengzhou, People’s Republic of China

Correspondence: [*] Correspondence to: Si Guo, Department of Medical laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China. E-mail: [email protected]. and Chuan-Yu Gao, Department of Cardiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China. E-mail: [email protected].

Note: [1] These authors have contributed equally to this work.

Abstract: Vascular dementia (VaD) is caused by chronic decreases in brain blood flow and accounts for 15–20% of dementia cases worldwide. In contrast to Alzheimer’s disease (AD), no effective drug treatments are currently available for VaD. Previous studies have suggested that oxidative stress and neuroinflammation in the brain play important roles in the pathogenesis of VaD. Honokiol (HKL) is a well-known bioactive and nutraceutical compound that can act as an antioxidant and anti-inflammatory molecule. HKL can protect against memory impairments in AD mouse models. In this study, we explored whether the application of HKL was also protective against the insult of chronic cerebral hypoperfusion (CCH) in rats. We found that HKL supplementation prevented the memory impairments in the inhibitory avoidance step-down and Morris water maze tasks in CCH rats. HKL also suppressed the levels of oxidative stress and inflammation in CCH rats. Moreover, HKL prevented dendritic spines abnormalities in CCH rats. We also found that HKL inhibited the activity of GSK-3β, which may be critical for the neuroprotective activity of HKL. Thus, our study demonstrated the protective role of HKL in VaD.

Keywords: GSK-3β, Honokiol, inflammation, memory impairments, oxidative stress, vascular dementia

DOI: 10.3233/JAD-190324

Journal: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 97-108, 2019