Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation

WANG Kan; YANG Rong; CHEN Tuan-tuan; QIN Mei-rong; WANG Ping; KONG Ming-wang

doi:10.1007/s11655-022-3589-5

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Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation

Original Article | Updated：2023-04-27

- Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation
- Chinese Journal of Integrative Medicine Vol. 29, Issue 5, Pages: 413-423(2023)
- Affiliations：
  
  1.The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou (510006), China
  2.Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province (518033), China
  3.Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao SAR, China
  4.Key Laboratory of Cosmetics Monitoring and Evaluation, State Drug Administration, Shenzhen Institute for Drug Control, Shenzhen, Guangdong Province (518057), China
  5.The School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan(430065), China
- Author bio：
  
  Prof. KONG Ming-wang, E-mail: kongmw@hbtcm.edu.cn
- Funds：
- DOI：10.1007/s11655-022-3589-5
  CLC：
- Published：2023-05，
  
  Published Online：07 December 2022，
  
  Accepted：01 July 2022
Scan for full text
WANG Kan, YANG Rong, CHEN Tuan-tuan, et al. Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation. [J]. Chinese Journal of Integrative Medicine 29(5):413-423(2023)
DOI：

WANG Kan, YANG Rong, CHEN Tuan-tuan, et al. Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation. [J]. Chinese Journal of Integrative Medicine 29(5):413-423(2023) DOI： 10.1007/s11655-022-3589-5.

摘要

Abstract

Objective:

To explore the specific pharmacological molecular mechanisms of Kai Xin San (KXS) on treating Alzheimer's disease (AD) based on network pharmacology and experimental validation.

Methods:

The chemical compounds of KXS and their corresponding targets were screened using the Encyclopedia of Traditional Chinese Medicine (ETCM) database. AD-related target proteins were obtained from MalaCards database and DisGeNET databases. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis. Functional enrichment analysis predicted the potential key signaling pathways involved in the treatment of AD with KXS. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally

the predicted key signaling pathway was validated experimentally. Positioning navigation and space search experiments were conducted to evaluate the cognitive improvement effect of KXS on AD rats. Western blot was used to further examine and investigate the expression of the key target proteins related to the predicted pathway.

Results:

In total

38 active compounds and 469 corresponding targets of KXS were screened

and 264 target proteins associated with AD were identified. The compound-target-disease and PPI networks identified key active ingredients and protein targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested a potential effect of KXS in the treatment of AD via the amyloid beta (Aβ)-glycogen synthase kinase-3 beta (GSK3β)-Tau pathway. Molecular docking revealed a high binding affinity between the key ingredients and targets.

In vivo

KXS treatment significantly improved cognitive deficits in AD rats induced by Aβ

1-42

decreased the levels of Aβ

p-GSK3β

p-Tau and cyclin-dependent kinase 5

and increased the expressions of protein phosphatase 1 alpha (PP1A) and PP2A (

0.05 or

0.01).

Conclusion:

KXS exerted neuroprotective effects by regulating the Aβ-GSK3β-Tau signaling pathway

which provides novel insights into the therapeutic mechanism of KXS and a feasible pharmacological strategy for the treatment of AD.

关键词

Keywords

Kai Xin SanAlzheimer's diseaseTau proteinnetwork pharmacologymolecular dockingexperimental validationChinese medicine

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