Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification.
10.19540/j.cnki.cjcmm.20221209.401
- Author:
Ke-Zhen CAI
1
;
Qin ZHENG
1
;
Xu-Dong ZHU
2
;
Shao-Feng WEI
1
;
Meng-Qi WU
1
;
Hui XIONG
1
;
Hai-Ting ZHAO
1
Author Information
1. State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Key Laboratory of Modern Preparation of Chinese Medicine under Ministry of Education, Jiangxi University of Chinese Medicine Nanchang 330004, China.
2. Jiangxi Provincial Engineering Research Center for Drug and Medical Device Quality, NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Institute for Drug Control Nanchang 330029, China.
- Publication Type:Journal Article
- Keywords:
Alzheimer′s disease;
PI3K/Akt signaling pathway;
Sijunzi Decoction;
UPLC-Q-TOF-MS;
blood-entering components;
network pharmacology
- MeSH:
Animals;
Mice;
Rats;
Proto-Oncogene Proteins c-akt;
Network Pharmacology;
Alzheimer Disease/drug therapy*;
Molecular Docking Simulation;
Phosphatidylinositol 3-Kinases/genetics*;
Tandem Mass Spectrometry;
Drugs, Chinese Herbal/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(6):1620-1631
- CountryChina
- Language:Chinese
-
Abstract:
The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
