Systems Pharmacology Approach to Investigate the Mechanism of Kai-Xin-San in Alzheimer’s Disease

Frontiers in Pharmacology

Pharmacology

Hanzhong Ke¹  Honghai Hong²  Yumin Xu³  Huilin Li⁴  Qihui Wu⁵  Chuipu Cai⁵  Xinning Liu⁵  Dongli Li⁵  Yanfang Liao⁵  Yunxia Luo⁶  Qi Wang⁷  Jiansong Fang⁷  Shuhuan Fang⁷ 

[1] Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, United States;Department of Medicine, Harvard Medical School, Boston, MA, United States;Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Department of Encephalopathy First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China;Department of Endocrinology, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China;Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China;Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China;Department of Endocrinology, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China;Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China;Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China;

关键词: systems pharmacology;    Kai-Xin-San;    Alzheimer's disease;    cholinergic system;    neuroinflammation;   

DOI  :  10.3389/fphar.2020.00381

 received in 2019-11-28, accepted in 2020-03-12,  发布年份 2020

来源: Frontiers

【 摘 要 】

Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by cognitive dysfunction. Kai-Xin-San (KXS) is a traditional Chinese medicine (TCM) formula that has been used to treat AD patients for over a thousand years in China. However, the therapeutic mechanisms of KXS for treating AD have not been fully explored. Herein, we used a comprehensive network pharmacology approach to investigate the mechanism of action of KXS in the treatment of AD. This approach consists of construction of multiple networks and Gene Ontology enrichment and pathway analyses. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms obtained from the systems pharmacology-based analysis. As a result, 50 chemicals in KXS and 39 AD-associated proteins were identified as major active compounds and targets, respectively. The therapeutic mechanisms of KXS in treating AD were primarily related to the regulation of four pathology modules, including amyloid beta metabolism, tau protein hyperphosphorylation process, cholinergic dysfunction, and inflammation. In scopolamine-induced cognitive dysfunction mice, we validated the anti-inflammatory effects of KXS on AD by determining the levels of inflammation cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. We also found cholinergic system dysfunction amelioration of KXS is correlated with upregulation of the cholinergic receptor CHRNB2. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the underlying therapeutic mechanism of KXS for the treatment of AD.

【 授权许可】

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Copyright © 2020 Luo, Li, Liao, Cai, Wu, Ke, Liu, Li, Hong, Xu, Wang, Fang and Fang