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Abstract：
Urolithin A and B are gut metabolites of ellagic acid and ellagitannins associated with many beneficial effects. Evidence in vitro pointed to their potential as estrogenic modulators. However, both molecular mechanisms and biological targets involved in such activity are still poorly characterized, preventing a comprehensive understanding of their bioactivity in living organisms. This study aimed at rationally identifying novel biological targets underlying the estrogenic-modulatory activity of urolithins.
The work relies on an in silico/in vitro target fishing study coupling molecular modeling with biochemical and cell-based assays. Estrogen sulfotransferase and 17β-hydroxysteroid dehydrogenase are identified as potentially subject to inhibition by the investigated urolithins. The inhibition of the latter undergoes experimental confirmation either in a cell-free or cell-based assay, validating computational outcomes.
The work describes target fishing as an effective tool to identify unexpected targets of food bioactives detailing the interaction at a molecular level. Specifically, it described, for the first time, 17β-hydroxysteroid dehydrogenase as a target of urolithins and highlighted the need of further investigations to widen the understanding of urolithins as estrogen modulators in living organisms.
The work relies on an in silico/in vitro target fishing study coupling molecular modeling with biochemical and cell-based assays. Estrogen sulfotransferase and 17β-hydroxysteroid dehydrogenase are identified as potentially subject to inhibition by the investigated urolithins. The inhibition of the latter undergoes experimental confirmation either in a cell-free or cell-based assay, validating computational outcomes.
The work describes target fishing as an effective tool to identify unexpected targets of food bioactives detailing the interaction at a molecular level. Specifically, it described, for the first time, 17β-hydroxysteroid dehydrogenase as a target of urolithins and highlighted the need of further investigations to widen the understanding of urolithins as estrogen modulators in living organisms.
摘要：
尿石素A和B是与许多有益作用相关的鞣花酸和鞣花宁的肠代谢产物。体外证据表明它们作为雌激素调节剂的潜力。然而,参与这种活动的分子机制和生物学靶标仍然缺乏表征，防止全面了解它们在生物体中的生物活性。这项研究旨在合理地确定尿石素雌激素调节活性的新生物靶标。
这项工作依赖于将分子建模与生化和基于细胞的测定相结合的计算机/体外目标捕捞研究。雌激素磺基转移酶和17β-羟基类固醇脱氢酶被鉴定为可能受到所研究的尿石素的抑制。后者的抑制在无细胞或基于细胞的测定中经历实验确认,验证计算结果。
这项工作将目标捕捞描述为一种有效的工具，可以识别食品生物活性物质的意外目标，并在分子水平上详细说明相互作用。具体来说,它描述，第一次,17β-羟基类固醇脱氢酶作为尿石素的靶标，并强调需要进一步研究以扩大对尿石素作为活生物体中雌激素调节剂的理解。
这项工作依赖于将分子建模与生化和基于细胞的测定相结合的计算机/体外目标捕捞研究。雌激素磺基转移酶和17β-羟基类固醇脱氢酶被鉴定为可能受到所研究的尿石素的抑制。后者的抑制在无细胞或基于细胞的测定中经历实验确认,验证计算结果。
这项工作将目标捕捞描述为一种有效的工具，可以识别食品生物活性物质的意外目标，并在分子水平上详细说明相互作用。具体来说,它描述，第一次,17β-羟基类固醇脱氢酶作为尿石素的靶标，并强调需要进一步研究以扩大对尿石素作为活生物体中雌激素调节剂的理解。
