1. Mechanism of inhibition of TLR4/NFκB/NLRP3 inflammatory pathway against AD based on the network pharmacology of Erjing Pills.
- Author
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Zhang C, Lu M, Li C, Qi C, Lin Q, Huang L, and Ding H
- Subjects
- Humans, Signal Transduction drug effects, Anti-Inflammatory Agents pharmacology, Toll-Like Receptor 4 metabolism, Toll-Like Receptor 4 drug effects, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal therapeutic use, NF-kappa B metabolism, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Molecular Docking Simulation, Network Pharmacology methods
- Abstract
Alzheimer disease is an irreversible neurodegenerative disease, and its pathogenesis involves various mechanisms such as neuroinflammation and β-amyloid deposition. Erjing Pills can inhibit neuroinflammation by inhibiting toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3; however, qualitative analysis of the material basis is lacking. Therefore, it is necessary to analyze and explore the material basis of network pharmacology research. This study employed a multifaceted approach, including drug-like screening, molecular docking, and bioinformatic analysis. Preliminary screening identified 59 drug ingredients in Erjing Pills that met the Absorption, Distribution, Metabolism, Excretion and Toxicity screening criteria. Among these, 7 ingredients, including diosgenin, exhibited superior binding properties compared with the positive drugs in molecular docking. Gene ontology annotation and pathway analysis revealed their involvement in crucial biological processes, such as hormone response, insulin resistance, and steroid hormone biosynthesis signaling pathways, which are known for their anti-inflammatory and cognitive enhancement effects. A meta-analysis of relevant literature corroborated the anti-inflammatory activities of diosgenin and 5 other ingredients. These 5 ingredients, with diosgenin as a prominent candidate, exert anti-inflammatory effects by targeting key components of the toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3 inflammatory pathway, thereby presenting potential efficacy in the treatment of Alzheimer disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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