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

Article type: Research Article

Authors: Tan, Yan^{a; 1} | Zhang, Jiani^{a; 1} | Yang, Ke^{a; 1} | Xu, Zihui^a | Zhang, Huawei^a | Chen, Weihang^a | Peng, Tiantian^a | Wang, Xu^a | Liu, Zhaoheng^a | Wei, Peng^a | Li, Na^a | Zhang, Zhenqiang^{b; *} | Liu, Tonghua^{a; *} | Hua, Qian^{a; *}

Affiliations: [a] Beijing University of Chinese Medicine, Beijing, China | [b] Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China

Correspondence: [*] Correspondence to: Prof. Qian Hua, Beijing University of Chinese Medicine, Beijing, China. E-mails: hqianz@163.com, huaq@bucm.edu.cn. Prof. Tong-Hua Liu, Beijing University of Chinese Medicine, Beijing, China. E-mail: thliu@vip.163.com and Prof. Zhenqiang Zhang, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China. E-mail: zhang_zhenqiang@126.com.

Note: [1] These authors contributed equally to this work.

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-β protein precursor (AβPP) processing in vitro. Methods:AβPP, β-secretase (BACE1), and 99-amino acid C-terminal fragment of AβPP (C99) stably transfected cells were used for the tests of AβPP processing. The production of Aβ, activity of BACE1, neprilysin (NEP), and γ-secretase were assessed by ELISA, RT-PCR, and western blot. Results:By upregulating BACE1 activity, D1 increased Aβ production whereas decreased the ratio of Aβ42/Aβ40; by downregulating BACE1 activity and modulating the expression of γ-secretase, T2 decreased Aβ production and the ratio of Aβ42/Aβ40; by downregulating BACE1 activity, Q3 decreased Aβ production; H4 did not change Aβ production due to the simultaneously downregulation of BACE1 and NEP activity. Conclusion:Our study indicates that these four anti-stroke CHMs regulate AβPP processing through different mechanisms. Particularly, T2 with relatively simple components and prominent effect on AβPP processing may be a promising candidate for the treatment of AD.

Keywords: Alzheimer’s disease, amyloid-β, BACE1, γ-secretase, NEP, Traditional Chinese Medicine

DOI: 10.3233/JAD-210652

Journal: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 261-272, 2022