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

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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 (A β)-glycogen synthase kinase-3 beta (GSK3 β)-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 Aβ1-42, 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 (P<0.05 or P<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.

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Author information

Authors and Affiliations

  1. The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Kan Wang

  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

    Rong Yang & Tuan-tuan Chen

  3. Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao SAR, China

    Rong Yang

  4. Key Laboratory of Cosmetics Monitoring and Evaluation, State Drug Administration, Shenzhen Institute for Drug Control, Shenzhen, Guangdong Province, 518057, China

    Mei-rong Qin & Ping Wang

  5. The School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Ming-wang Kong

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  1. Kan Wang
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Contributions

Wang K and Yang R performed the experiments, acquired

Corresponding author

Correspondence to Ming-wang Kong.

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The authors declare no conflict of interest.

Additional information

Supported by the National Science and Technology Major Project of China (No. 2009ZX09103-347)

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Wang, K., Yang, R., Chen, Tt. et al. Therapeutic Mechanism of Kai Xin San on Alzheimer’s Disease Based on Network Pharmacology and Experimental Validation. Chin. J. Integr. Med. 29, 413–423 (2023). https://doi.org/10.1007/s11655-022-3589-5

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