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.

中文翻译：

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结合网络药理学和实验验证探明芦笋抗氟中毒脑损伤的作用机制


芦笋(ASP)具有抗氧化、抗炎、抗衰老和增强免疫系统的作用。我们通过网络药理学和体内实验验证探讨了 ASP 对氟中毒引起的脑损伤的预防和治疗作用。我们从Traditional Chinese Medicine Systems Pharmacology数据库中确定了ASP的药物活性成分和药物靶点，利用GeneCards和Online Mendelian Inheritance in Man数据库预测了氟中毒脑损伤的疾病靶点，在Search中获得了靶蛋白-蛋白相互作用网络相互作用基因/蛋白质数据库检索工具，使用Cytoscape获取关键靶点和活性成分，并对数据库中的关键靶点进行注释、可视化和集成发现的富集分析。富集分析表明，“丝裂原激活蛋白激酶”(MAPK)、“磷酸肌醇 3-激酶/蛋白激酶 B”(PI3K-Akt)、“核因子-κ B”(NF-κB) 和“神经营养因子信号通路” ”是最丰富的生物过程和信号通路。 ASP可以减轻氟中毒损伤，改善脑组织损伤，增加尿氟含量，改善体内氧化水平和炎症因子水平。 ASP 还可以减少氟斑牙、骨骼损伤、血液和骨骼中的氟化物浓度以及过氧化脂质的积累。 ASP 治疗后，大鼠沉默信息调节因子 (SIRT)1、脑源性神经营养因子 (BDNF)、原肌球蛋白受体激酶 B (TrkB)、MAPK、NF-κB、PI3K、Akt 和 B 细胞淋巴瘤-2 的表达脑组织逐渐增多，而Bax、caspase-3、p53逐渐减少。 我们证明了ASP可以通过SIRT1/BDNF/TrkB信号通路调节氟中毒引起的脑损伤，并报道了ASP在预防和治疗氟中毒中可能发挥的作用。