Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Zhengzhou University, People’s Republic of China | [b] Medical Research Center, The First Affiliated Hospital of Zhengzhou University, People’s Republic of China
Correspondence:
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Correspondence to: Chen Chen, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Number 1 Jian She Dong Avenue, Zhengzhou City 450002, Henan Province, People’s Republic of China. E-mail: [email protected].
Abstract: Vascular dementia (VaD) is the second most common dementia worldwide. Unlike Alzheimer’s disease, VaD does not yet have effective therapeutic drugs. Harpagoside is the most important component extracted from Harpagophytum procumbens, a traditional Chinese medicine that has been widely used. The neuroprotective effects of harpagoside have been studied in Aβ- and MPTP-induced neurotoxicity. However, whether harpagoside is protective against VaD is not clear. In this study, with the use of chronic cerebral hypoperfusion rats, a well-known VaD model, we demonstrated that chronic administration (two months) of harpagoside was able to restore both the spatial learning/memory and fear memory impairments. Importantly, the protective effects of harpagoside were not due to alterations in the physiological conditions, metabolic parameters, or locomotor abilities of the rats. Meanwhile, we found that harpagoside suppressed the overactivation of PTEN induced by CCH by enhancing PTEN phosphorylation. Furthermore, harpagoside elevated the activity of Akt and inhibited the activity of GSK-3β, downstream effectors of PTEN. Overall, our study suggested that harpagoside treatment might be a potential therapeutic drug targeting the cognitive impairments of VaD.
