Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
Neurochem Res. 2021 May;46(5):1068-1080. doi: 10.1007/s11064-021-03235-y. Epub 2021 Mar 8.
Alzheimer's disease (AD) process is characterized classically by two hallmark pathologies: β-amyloid (Aβ) plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Aβ peptides play an important role in AD, but despite much effort the molecular mechanisms of how Aβ contributes to AD remain unclear. The present study evaluated the effects of the active components of Epimedium, Astragalus and Radix Puerariae induced HAMP on key enzymes in the hydrolysis of APP in HT22 cells. The active components of Epimedium, Astragalus and Radix Puerariae could effectively up-regulate the expression of HAMP, alleviate the iron overload in the brain tissues of mice, significantly improve the learning and memory ability of AD, down-regulate the expression of Aβ and reduce the deposition of SP in an APPswe/PS1 transgenic mouse model of AD. HAMP and Aβ induced HT22 cells are used as AD cell models in this study to investigate the effect of the compound consisting of the effective components of Epimedium, Astragalus and Pueraria on the key enzymes in the hydrolysis of APP. After the administration of traditional Chinese medicine (TCM), the expression levels of ADAM10 and ADAM17 were increased while the expression level of BACE1 decreased. This indicates that TCM can promote the expression level of ADAM10 and ADAM17, inhibit the expression level of BACE1, thus further inhibiting the production of amyloid protein and reducing the production of Aβ and SP. Compared with RNAi group, the expression level of ADAM10 and ADAM17 in Aβ + RNAi group was decreased while the expression level of BACE1 increased. Compared with the Aβ + RNAi group the expression level of ADAM10 and ADAM17 in the Aβ + RNAi + TCM group was increased while the expression level of BACE1 was decreased. The present study indicated the effects of the active components of Epimedium, Astragalus and Radix Puerariae may alleviate AD by up-regulating the expression of HAMP, thus reducing brain iron overload, promoting the expression of ADAM10 and ADAM17, inhibiting the expression of BACE1, and reducing the deposition of Aβ.
阿尔茨海默病（AD）的过程经典地以两种标志性病理学为特征：β-淀粉样蛋白（Aβ）斑块沉积和过度磷酸化 tau 的神经原纤维缠结。Aβ 肽在 AD 中起重要作用，但尽管付出了很多努力，Aβ 如何导致 AD 的分子机制仍不清楚。本研究评估了淫羊藿、黄芪和葛根的活性成分诱导 HAMP 对 HT22 细胞中 APP 水解的关键酶的影响。淫羊藿、黄芪和葛根的活性成分可有效上调 HAMP 的表达，减轻小鼠脑组织中的铁过载，显著改善 AD 的学习记忆能力，下调 Aβ的表达，减少 AD APPswe/PS1 转基因小鼠模型中 SP 的沉积。本研究中使用 HAMP 和 Aβ 诱导的 HT22 细胞作为 AD 细胞模型，研究由淫羊藿、黄芪和葛根的有效成分组成的化合物对 APP 水解关键酶的影响。给药后，ADAM10 和 ADAM17 的表达水平增加，而 BACE1 的表达水平降低。这表明中药可以促进 ADAM10 和 ADAM17 的表达水平，抑制 BACE1 的表达水平，从而进一步抑制淀粉样蛋白的产生，减少 Aβ和 SP 的产生。与 RNAi 组相比，Aβ+RNAi 组中 ADAM10 和 ADAM17 的表达水平降低，而 BACE1 的表达水平升高。与 Aβ+RNAi 组相比，Aβ+RNAi+TCM 组中 ADAM10 和 ADAM17 的表达水平升高，而 BACE1 的表达水平降低。本研究表明，淫羊藿、黄芪和葛根的活性成分可能通过上调 HAMP 的表达来缓解 AD，从而减轻脑铁过载，促进 ADAM10 和 ADAM17 的表达，抑制 BACE1 的表达，减少 Aβ的沉积。
