Combining Network Pharmacology and Experimental Verification to Ascertain the Mechanism of Action of Asparagus officinalis Against the Brain Damage Caused by Fluorosis

ABSTRACT Asparagus officinalis (ASP) has antioxidation, anti‐inflammatory, antiaging, and immune system‐enhancing effects. We explored the preventive and therapeutic consequences of ASP on the brain damage elicited by fluorosis through network pharmacology and in vivo experimental validation. We ascertained the pharmaceutically active ingredients and drug targets of ASP from the Traditional Chinese Medicine Systems Pharmacology database, predicted the disease targets of fluorosis‐induced brain injury using GeneCards and Online Mendelian Inheritance in Man databases, obtained target protein–protein interaction networks in the Search Tool for the Retrieval of Interacting Genes/Proteins database, used Cytoscape to obtain key targets and active ingredients, and conducted enrichment analyses of key targets in the Database for Annotation, Visualization and Integrated Discovery. Enrichment analyses showed that “mitogen‐activated protein kinase” (MAPK), “phosphoinositide 3‐kinase/protein kinase B” (PI3K‐Akt), “nuclear factor‐kappa B” (NF‐κB), and the “neurotrophin signaling pathway” were the most enriched biological processes and signaling pathways. ASP could alleviate fluorosis‐based injury, improve brain‐tissue damage, increase urinary fluoride content, and improve oxidation levels and inflammatory‐factor levels in the body. ASP could also reduce dental fluorosis, bone damage, fluoride concentrations in blood and bone, and accumulation of lipid peroxide. Upon ASP treatment, expression of silent information regulator (SIRT)1, brain‐derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), MAPK, NF‐κB, PI3K, Akt, and B‐cell lymphoma‐2 in rat brain tissue increased gradually, whereas that of Bax, caspase‐3, and p53 decreased gradually. We demonstrated that ASP could regulate the brain damage caused by fluorosis through the SIRT1/BDNF/TrkB signaling pathway, and reported the possible part played by ASP in preventing and treating fluorosis.