Department of Neurology, The First Affiliated Hospital of Zhengzhou University, People's Republic of China.
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, People's Republic of China.
J Alzheimers Dis. 2018;63(2):445-455. doi: 10.3233/JAD-171170.
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.
血管性痴呆（VaD）是全球第二常见的痴呆症。与阿尔茨海默病不同，VaD 目前尚无有效的治疗药物。裂环烯醚萜苷是从传统中药虎杖中提取的最重要成分，已被广泛应用。裂环烯醚萜苷对 Aβ 和 MPTP 诱导的神经毒性具有神经保护作用。然而，裂环烯醚萜苷是否对 VaD 具有保护作用尚不清楚。在这项研究中，我们使用慢性脑低灌注大鼠，一种众所周知的 VaD 模型，证明了裂环烯醚萜苷的慢性给药（两个月）能够恢复空间学习/记忆和恐惧记忆障碍。重要的是，裂环烯醚萜苷的保护作用不是由于大鼠的生理状况、代谢参数或运动能力的改变。同时，我们发现裂环烯醚萜苷通过增强 PTEN 磷酸化抑制 CCH 引起的 PTEN 过度激活。此外，裂环烯醚萜苷还能提高 Akt 的活性并抑制 GSK-3β的活性，PTEN 的下游效应物。总的来说，我们的研究表明，裂环烯醚萜苷治疗可能是一种针对 VaD 认知障碍的潜在治疗药物。
