Researches on molecular mechanism of Dihuang Yinzi Decoction for application to Alzheimer's disease from regulation of apoptotic network / 中草药

ABSTRACT

Objective: To confirm evidence regarding the potential therapeutic effect of Dihuang Yinzi Decoction (DHYZ) on Alzheimer's disease (AD) from the regulation of apoptotic network using network pharmacology and molecular biology. Methods: The active ingredients of DHYZ were screened and the potential therapeutic targets on AD were predicted, and the drug-target-disease network and protein-protein interactions (PPI) network were built by using network pharmacology. The main targets and signaling pathways of apoptotic networks of DHYZ were performed by bioinformatics analysis. AD cell model was bulit by Aβ1-42 treating serum containing different concentrations. The cell viability was detected by MTT assay. The cell apoptosis was detected by flow cytometry. The cell apoptosis related gene and protein express were detected by qPCR and Western blotting. Results: A total of 108 active ingredients of DHYZ were screened out, and 222 potential therapeutic targets for AD were predicted by network pharmacology. Among the 222 potential therapeutic targets, 202 of them had 3 737 kinds of PPI network, which were closely related to the apoptotic network signaling pathways and biological processes regulation, involving TNF, AKT1, MAPK3, NFKB1, TP53, CASP3, etc. The predicted results were verified by qPCR and Western blotting. Meanwhile, cell experiments showed that DHYZ contained serum of different concentrations inhibited apoptosis of Aβ1-42-induced SH-SY5Y cells in a concentration-dependent, which was related to the regulation of apoptosis related genes and proteins. Conclusion: The results indicated that the active compounds in DHYZ interact with apoptosis-related multiple targets and multiple pathways, which is an important mechanism of DHYZ for application to AD.