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/PS1ΔE9 transgenic mouse model of AD. HAMP and Aβ25-35 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.
Keywords: ADAM10; ADAM17; BACE1; HAMP; Traditional Chinese medicine.