关键词: Drosophila melanogaster compound absorption compound excretion isoflavone phytoestrogen phytogenic drugs

Mesh : Animals Drosophila melanogaster / drug effects metabolism Phytoestrogens / pharmacokinetics pharmacology Male Female Isoflavones / pharmacokinetics pharmacology Biological Availability Sex Characteristics Administration, Oral

来  源:   DOI:10.1016/j.biopha.2024.116612

Abstract:
Drosophila melanogaster, or the fruit fly, is widely used for modeling numerous human diseases, such as neurodegeneration, tumor development, cachexia, and intestinal dysfunction. It is a suitable model organism for research targeting the physiology and pathophysiology of the intestinal epithelial barrier and has also been used as a model organism for preliminary drug and bioactive nutrient screening. However, the application of D. melanogaster in research on drug bioavailability and pharmacokinetic properties has not yet been well explored. In this study, we applied D. melanogaster to investigate the absorption and excretion of the orally administered phytoestrogens daidzein, glycitein, genistein, and their glycosides. Therefore, we established a quick, noninvasive method to quantify compound retention in D. melanogaster, suitable for the investigation of a broad variety of potentially bioactive substances. We showed that fruit fly sex plays a key role in the metabolization, transportation, and excretion of phytoestrogenic isoflavones. In particular, female fruit flies retained significantly more isoflavones than male fruit flies, which was reflected in the greater metabolic impact of isoflavones on females. Male fruit flies excreted more isoflavones than females did, which was linked to the upregulation of the xenobiotic transporter gene Mdr50. We also demonstrated that micellized isoflavones were more bioavailable than powdered isoflavones, independent of sex, age or the addition of dietary fibers.
摘要:
黑腹果蝇,或者果蝇,广泛用于模拟许多人类疾病,比如神经变性,肿瘤发展,恶病质,和肠道功能障碍。它是针对肠上皮屏障的生理学和病理生理学进行研究的合适模型生物,也已被用作初步药物和生物活性营养素筛选的模型生物。然而,在药物生物利用度和药代动力学研究中的应用尚未得到很好的探索。在这项研究中,我们应用D.melanogaster研究口服植物雌激素大豆苷元的吸收和排泄,糖素,Genistein,和它们的糖苷。因此,我们建立了一个快速的,非侵入性的方法来量化在黑腹D中的化合物滞留,适用于调查各种潜在的生物活性物质。我们发现果蝇的性别在新陈代谢中起着关键作用,交通运输,和植物雌激素异黄酮的排泄。特别是,雌性果蝇比雄性果蝇保留更多的异黄酮,这反映在异黄酮对女性的代谢影响更大。雄性果蝇比雌性果蝇分泌更多的异黄酮,这与异种生物转运蛋白基因Mdr50的上调有关。我们还证明了胶束化的异黄酮比粉末异黄酮更具生物可利用性,与性无关,年龄或添加膳食纤维。
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