Anti-Stroke Chinese Herbal Medicines Inhibit Abnormal Amyloid-ß Protein Precursor Processing in Alzheimer's Disease.

ABSTRACT

BACKGROUND: Chinese Herbal Medicines (CHMs), as an important and integral part of a larger system of medicine practiced in China, called Traditional Chinese Medicine (TCM), have been used in stroke therapy for centuries. A large body of studies suggest that some Chinese herbs can help reverse cognitive impairment in stroke patients, while whether these herbs also exert therapeutic benefits for Alzheimer's disease remains to be seen. OBJECTIVE: To address this issue, we selected four types of CHMs that are commonly prescribed for stroke treatment in clinical practice, namely DengZhanXiXin (D1), TongLuoJiuNao (T2), QingKaiLing (Q3), and HuangQinGan (H4), and tested their effects on amyloid-ß protein precursor (AßPP) processing in vitro. METHODS: AßPP, ß-secretase (BACE1), and 99-amino acid C-terminal fragment of AßPP (C99) stably transfected cells were used for the tests of AßPP processing. The production of Aß, activity of BACE1, neprilysin (NEP), and γ-secretase were assessed by ELISA, RT-PCR, and western blot. RESULTS: By upregulating BACE1 activity, D1 increased Aß production whereas decreased the ratio of Aß42/Aß40; by downregulating BACE1 activity and modulating the expression of γ-secretase, T2 decreased Aß production and the ratio of Aß42/Aß40; by downregulating BACE1 activity, Q3 decreased Aß production; H4 did not change Aß production due to the simultaneously downregulation of BACE1 and NEP activity. CONCLUSION: Our study indicates that these four anti-stroke CHMs regulate AßPP processing through different mechanisms. Particularly, T2 with relatively simple components and prominent effect on AßPP processing may be a promising candidate for the treatment of AD.