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

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-beta protein precursor (A beta PP) processing in vitro. Methods: A beta PP, beta-secretase (BACE1), and 99-amino acid C-terminal fragment of A beta PP (C99) stably transfected cells were used for the tests of A beta PP processing. The production of A beta, activity of BACE1, neprilysin (NEP), and gamma-secretase were assessed by ELISA, RT-PCR, and western blot. Results: By upregulating BACE1 activity, D1 increased A beta production whereas decreased the ratio of A beta(42)/A beta(40); by downregulating BACE1 activity and modulating the expression of gamma-secretase, T2 decreased A beta production and the ratio of A beta(42)/A beta(40); by downregulating BACE1 activity, Q3 decreased A beta production; H4 did not change A beta production due to the simultaneously downregulation of BACE1 and NEP activity. Conclusion: Our study indicates that these four anti-stroke CHMs regulate A beta PP processing through different mechanisms. Particularly, T2 with relatively simple components and prominent effect on A beta PP processing may be a promising candidate for the treatment of AD.

Automated summary

This study found that these four anti-stroke CHMs regulate A beta PP processing through different mechanisms, with T2 being a promising candidate for AD treatment.