| 作者单位 |
College of Pharmacy, Guilin Medical University； Department of Nephrology,Guilin Municipal Hospital of Traditional Chinese Medicine； Guangxi Key Laboratory of Drug Discovery and Optimization, Guilin Medical University； Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, College of Pharmacy, Guilin Medical University |
| 摘要 |
[Objectives] To explore the possible targets of Huanglian Jiedu Decoction in NLRP3/IFITM3/γ-secretase pathway through regulating iron homeostasis and the potential mechanism of anti-Alzheimer’s disease (AD). [Methods] Firstly, the active components and related targets of Huanglian Jiedu Decoction were predicted in the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the targets of AD were collected from Genecards, OMIM and MalaCards databases. Genes inhibiting iron homeostasis were obtained from the ferroptosis Database (FerrDB). Then, Huanglian Jiedu Decoction the interactive genes of the active component target, the AD target and the iron homeostasis target. Next, the protein-protein interaction (PPI) network of interactive genes was constructed, and the software Cytoscape 3.9.1 was used to visualize and screen out the key active components and target genes. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. [Results] A total of 51 Huanglian Jiedu Decoction components and 247 potential protein targets were identified, including 1942 AD targets, 369 iron homeostasis regulatory genes, and 18 intersection targets. Eleven key targets including CDKN2A, MAPK1, TGFβ1, MAPK14, TP53, EGFR, GSK3β, PTEN, HIF1α, HMOX1 and PRKCα were identified by PPI network analysis. [Conclusions] In the regulation of iron homeostasis in AD by Huanglian Jiedu Decoction, CDKN2A, MAPK1, TGFβ1, MAPK14, TP53, EGFR, GSK3β, PTEN, HIF1α, HMOX1 and PRKCα may be involved, involving ErbB signaling pathway, endocrine resistance signaling pathway, HIF-1 signaling pathway and so on. |
