kaempferol 3-O-glucuronide | 22688-78-4

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: kaempferol 3-O-glucuronide
• 英文别名: kaempferol-3-glucuronide；kaempferol 3-O-glucoronide；kaempferol glucuronide；(2S,3S,4S,5R)-6-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 22688-78-4
• 化学式: C₂₁H₁₈O₁₂
• 分子量: 462.367
• InChiKey: FNTJVYCFNVUBOL-MBIBTLSJSA-N

物化性质

• 熔点：
  189-191 °C
• 沸点：
  876.8±65.0 °C(Predicted)
• 密度：
  1.87
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  2.300 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  203
• 氢给体数：
  7
• 氢受体数：
  12

ADMET

代谢

Kaempferol-3-glucuronide 是 Kaempferol 的已知人体代谢物。

Kaempferol-3-glucuronide is a known human metabolite of Kaempferol.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38

制备方法与用途

生物活性 Kaempferol 3-O-β-D-glucuronide（山奈酚-3-葡萄糖苷）是一种结合代谢产物，具有显著的抗炎作用。它能够显著抑制多种促炎介质，如 IL-1β、NO、PGE2 和 LTB4，并上调抗炎细胞因子 IL-10 的分泌。

靶点

IL-1β
IL-10

反应信息

• 作为产物：
  描述：

  山奈酚 、 6-[[[5-(2,4-二氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-3,4,5-三羟基四氢吡喃-2-羧酸 在 D-Saccharic acid 1,4-lactone 、 alamethicin I 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.33h， 生成 kaempferol 3-O-glucuronide
  参考文献：
  名称：

  Interplay of Efflux Transporters with Glucuronidation and Its Impact on Subcellular Aglycone and Glucuronide Disposition: A Case Study with Kaempferol

  摘要：

  Glucuronidation is a major process of drug metabolism and elimination that generally governs drug efficacy and toxicity. Publications have demonstrated that efflux transporters control intracellular glucuronidation metabolism. However, it is still unclear whether and how efflux transporters interact with UDP-glucuronosyltransferases (UGTs) in sub-cellular organelles. In this study, kaempferol, a model fluorescent flavonoid, was used to investigate the interplay of glucuronidation with transport at the subcellular level. Human recombinant UGTs and microsomes were utilized to characterize the in vitro glucuronidation kinetics of kaempferol. The inhibition of UGTs and efflux transporters on the sub cellular disposition of kaempferol were determined visually and quantitatively in Caco-2/TC7 cells. The knockout of transporters on the subcellular accumulation of kaempferol in liver and intestine were evaluated visually. ROS and Nrf2 were assayed to evaluate the pharmacological activities of kaempferol. The results showed that UGT1A9 is the primary enzyme responsible for kaempferol glucuronidation. Visual and quantitative data showed that the UGT1A9 inhibitor carvacrol caused a significant rise in subcellular aglycone and reduction in subcellular glucuronides of kaempferol. The inhibition and knockout of transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs), exhibited a marked increase in subcellular kaempferol and decrease in its subcellular glucuronides. Correspondingly, inhibition of UGT1A9 and transporters led to increased kaempferol and, consequently, a significantly enhanced ROS scavenging efficiency and nuclear translocation of Nrf2. In conclusion, the interplay of efflux transporters (P-gp, BCRP, and MRPs) and UGTs govern the subcellular exposure and corresponding pharmacological activity of kaempferol.

  DOI：

  10.1021/acs.molpharmaceut.8b00782

文献信息

• Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches
  作者：Baojian Wu、Xiaoqiang Wang、Shuxing Zhang、Ming Hu

  DOI：10.1007/s11095-012-0666-z

  日期：2012.6

  Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2  = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2  = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。
• [EN] COMPOSITIONS COMPRISING UROLITHINS AND USES THEREOF FOR THE STIMULATION OF INSULIN SECRETION<br/>[FR] COMPOSITIONS COMPRENANT DES UROLITHINES, ET LEURS UTILISATIONS POUR LA STIMULATION DE SÉCRÉTION D'INSULINE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2015055736A1

  公开（公告）日：2015-04-23

  The present invention relates to a composition comprising urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion, and to the use of a compound chosen among urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, intended for the stimulation of insulin secretion. The present invention also relates to a composition comprising an effective amount of urolithin B, urolithin C, urolithin D, or a combination thereof, for the treatment or the prevention of diabetes mellitus, and in particular for the treatment or the prevention of type 2 diabetes, and to the use of a compound chosen among urolithin B, urolithin C, urolithin D, and a combination thereof, intended for the treatment or the prevention of diabetes mellitus, and in particular of type 2 diabetes.

  本发明涉及一种包含乌罗利酸A、乌罗利酸B、乌罗利酸C、乌罗利酸D或其组合的组合物，用于刺激胰岛素分泌，并且涉及使用从乌罗利酸A、乌罗利酸B、乌罗利酸C、乌罗利酸D或其组合中选择的化合物，用于刺激胰岛素分泌。本发明还涉及一种包含有效量的乌罗利酸B、乌罗利酸C、乌罗利酸D或其组合的组合物，用于治疗或预防糖尿病，特别是用于治疗或预防2型糖尿病，并且涉及使用从乌罗利酸B、乌罗利酸C、乌罗利酸D或其组合中选择的化合物，用于治疗或预防糖尿病，特别是2型糖尿病。
• Compositions comprising urolithins and uses thereof for the stimulation of insulin secretion
  申请人：Centre National de la Recherche Scientifique (CNRS)

  公开号：EP2862568A1

  公开（公告）日：2015-04-22

  The present invention relates to a composition comprising an effective amount of urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion, and to the use of a compound chosen among urolithin A, urolithin B, urolithin C, urolithin D, or a combination thereof, for the stimulation of insulin secretion. The present invention also relates to a composition comprising an effective amount of urolithin B, urolithin C, urolithin D, or a combination thereof, for the treatment or the prevention of diabetes mellitus, and to the use of a compound chosen among urolithin B, urolithin C, urolithin D, and a combination thereof, for the treatment or the prevention of diabetes mellitus.

  本发明涉及一种组合物，包括有效量的尿石素A、尿石素B、尿石素C、尿石素D或其组合，用于刺激胰岛素分泌，并且涉及从尿石素A、尿石素B、尿石素C、尿石素D或其组合中选择一种化合物，用于刺激胰岛素分泌的用途。 本发明还涉及一种组合物，包括有效量的尿石素B、尿石素C、尿石素D或其组合，用于治疗或预防糖尿病，并且涉及从尿石素B、尿石素C、尿石素D或其组合中选择一种化合物，用于治疗或预防糖尿病的用途。
• Methodologies for improving the quality of meat, health status of animals and impact on environment
  申请人：Aarhus Universitet

  公开号：EP2289348A2

  公开（公告）日：2011-03-02

  Disclosed is a method and a product of a chicory root product for reducing taint in animals, said method comprising feeding to an animal a chicory root product during at least one day prior to slaughtering the animal. By feeding animals with the chicory root product this improves the quality of meat, prevents or reduces female and male animal taint, primarily boar taint caused by skatole and/or androstenone. The invention also relates to methods for improving the health status of animals e.g. by reducing infections by pathogens in the gastrointestinal tract and to methods for reducing animal caused odours in general. The chicory root product comprises inulin/fructan (fructooligosaccarides) other low molecular weight sugars and secondary metabolites.

  本发明公开了一种用于减少动物污点的菊苣根产品的方法和产品，所述方法包括在屠宰动物前至少一天给动物喂食菊苣根产品。通过给动物喂食菊苣根产品，可以提高肉的质量，防止或减少雌性和雄性动物的污点，主要是由斯卡托尔和/或雄烯酮引起的公猪污点。本发明还涉及改善动物健康状况的方法，例如通过减少胃肠道中病原体的感染，以及减少动物引起的一般气味的方法。菊苣根产品包括菊粉/果聚糖（fructooligosaccarides）、其他低分子量糖类和次生代谢物。
• Glycan therapeutics and related methods thereof
  申请人：KALEIDO BIOSCIENCES, INC.

  公开号：US10314853B2

  公开（公告）日：2019-06-11

  Preparations of glycan therapeutics, pharmaceutical compositions and medical foods thereof, optionally comprising micronutrients, polyphenols, prebiotics, probiotics, or other agents are provided and methods of making same. Also provided are methods of using said gycan therapeutics, e.g. for the modulation of human gastrointestinal microbiota and to treat dysbioses.

  本发明提供了可选择包含微量营养素、多酚、益生元、益生菌或其他制剂的聚糖疗法制剂、药物组合物及其医用食品，以及制造方法。还提供了使用所述糖治疗剂的方法，例如用于调节人类胃肠道微生物群和治疗菌群失调。