Molecular Modeling Laboratory, Department of Food Science, University of Parma, Parco Area delle Scienze 95/A, 43125 Parma, Italy.
Food Funct. 2013 Oct;4(10):1442-51. doi: 10.1039/c3fo60117j.
Estrogen Receptors (ERs) are ligand-dependent intracellular transcriptional factors involved in many diseases. ERs mediate many of the effects of estrogens, but also exogenous compounds are able to interfere with ER, disrupting endocrine signaling. Among these xenobiotics, compounds present in food and feed make ERs a relevant target in the context of dietary modulation of health. In this sense, urolithins, gut microbiota derived metabolites of plant polyphenolic ellagitannins, may represent good candidates to act as phytoestrogens that are able to modulate the activity of ERs. An in silico method to qualitatively evaluate the potential xenoestrogenic agonistic behavior of ellagitannin-derived metabolites is proposed. The "full-dry" in silico approach involved structure based virtual screening (SBVS), docking simulations and re-scoring procedures. Results provided valuable insights about the phase II conjugations (glucuronidation, sulfation, and methylation, occurring in vivo) affecting the estrogenicity of these compounds on α- and β-ER isoforms. Hydroxylation patterns also revealed a significant role in the agonistic behavior of urolithin derivatives. On the whole, ellagitannin-derived metabolites exerted different predicted xenoestrogenic activity depending on chemical structures, and the applied in silico approach may represent a successful and easy choice to analyze enormous datasets of food-related compounds in order to understand their potential biological features.
雌激素受体（ERs）是配体依赖性的细胞内转录因子，参与多种疾病。ERs 介导了许多雌激素的作用，但外源性化合物也能够干扰 ER，破坏内分泌信号。在这些外来化合物中，存在于食物和饲料中的化合物使 ER 成为饮食调节健康的相关靶点。在这种情况下，植物多酚鞣花单宁的肠道微生物衍生代谢物尿石素，可能是作为能够调节 ER 活性的植物雌激素的良好候选物。本文提出了一种定性评估鞣花单宁衍生代谢物潜在的类雌激素激动作用的计算方法。“全干”计算方法包括基于结构的虚拟筛选（SBVS）、对接模拟和重新评分程序。结果为这些化合物在体内发生的 II 期共轭（葡糖醛酸化、硫酸化和甲基化）对 α-和 β-ER 同工型的雌激素活性提供了有价值的见解。羟基化模式也揭示了尿石素衍生物激动作用中的重要作用。总的来说，鞣花单宁衍生代谢物的类雌激素活性因化学结构而异，所应用的计算方法可能是分析与食物相关的大量化合物的数据集以了解其潜在生物学特征的一种成功且简单的选择。
