α-punicalagin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: α-punicalagin
• 英文别名: punicalagin α；(1R,35R,37S,38R,55S)-6,7,8,11,12,23,24,27,28,29,37,43,44,45,48,49,50-heptadecahydroxy-2,14,21,33,36,39,54-heptaoxaundecacyclo[33.20.0.04,9.010,19.013,18.016,25.017,22.026,31.038,55.041,46.047,52]pentapentaconta-4,6,8,10,12,16,18,22,24,26,28,30,41,43,45,47,49,51-octadecaene-3,15,20,32,40,53-hexone
• 化学式: C₄₈H₂₈O₃₀
• 分子量: 1084.73
• InChiKey: ZJVUMAFASBFUBG-OGJBWQGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  78
• 可旋转键数：
  0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  511
• 氢给体数：
  17
• 氢受体数：
  30

ADMET

代谢

石榴，一种原产于中东的水果，已经作为一种功能食品和营养保健源在全球范围内获得了广泛的流行。整果以及其果汁和提取物的健康效果已经针对多种慢性疾病进行了研究。来自人类临床试验的数据显示，石榴对心血管疾病、糖尿病和前列腺癌具有积极效果。石榴的体外抗氧化活性归功于其高含量的多酚类化合物，特别是石榴酸、石榴素、没食子酸和鞣花酸。这些化合物在消化过程中被代谢为鞣花酸和尿石素，这表明提供体内抗氧化活性的生物活性化合物可能与完整食物中存在的化合物不同……

Pomegranate, a fruit native to the Middle East, has gained widespread popularity as a functional food and nutraceutical source. The health effects of the whole fruit, as well as its juices and extracts, have been studied in relation to a variety of chronic diseases. Promising results against cardiovascular disease, diabetes, and prostate cancer have been reported from human clinical trials. The in vitro antioxidant activity of pomegranate has been attributed to its high polyphenolic content, specifically punicalagins, punicalins, gallagic acid, and ellagic acid. These compounds are metabolized during digestion to ellagic acid and urolithins, suggesting that the bioactive compounds that provide in vivo antioxidant activity may not be the same as those present in the whole food...

来源:Hazardous Substances Data Bank (HSDB)

代谢

石榴已经显示出含有124种不同的植物化学物质，其中一些共同作用，对癌细胞发挥抗氧化和抗炎效果。鞣花酸是石榴中存在的生物活性多酚。通过压榨整个水果获得的石榴汁比任何常见饮用的果汁含有更高的鞣花酸浓度，并且含有独特的鞣花酸，即石榴鞣花酸。石榴鞣花酸是已知分子量最大的多酚。石榴鞣花酸不会完整地被血液吸收，而是在小肠中经过数小时水解成鞣花酸。鞣花酸也被肠道菌群代谢成尿石酸，这些尿石酸在肝脏结合后通过尿液排出。这些尿石酸也具有生物活性，并能抑制前列腺癌细胞的生长...

Pomegranates have been shown to contain 124 different phytochemicals, and some of them act in concert to exert antioxidant and anti-inflammatory effects on cancer cells. Ellagitannins are bioactive polyphenols present in pomegranate. Pomegranate juice obtained by squeezing the whole fruit has the highest concentration of ellagitannins than any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the known largest molecular weight polyphenol. Pomegranate ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid over several hours in the intestine. Ellagitannins are also metabolized into urolithins by gut flora, which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth...

来源:Hazardous Substances Data Bank (HSDB)

代谢

腹膜内和口服合成的尿石素A导致前列腺组织中摄取尿石素A及其结合物，且前列腺、结肠和肠组织的水平相对于其他器官更高。目前尚不清楚为什么石榴鞣花单宁代谢物在前列腺、结肠和肠组织中的水平相对于研究中其他器官更高。重要的是，生物活性的石榴鞣花单宁代谢物倾向于定位于前列腺组织，结合临床数据表明石榴汁具有抗癌效果，这提示石榴产品可能在前列腺癌化学预防中发挥作用。长期服用石榴汁或石榴提取物后，人前列腺组织中的尿石素是否可以作为生物标志物仍有待确定。

Intraperitoneal and oral administration of synthesized urolithin A led to uptake of urolithin A and its conjugates in prostate tissue, and levels were higher in prostate, colon, and intestinal tissues relative to other organs. It is unclear why pomegranate ellagitannins metabolites localize at higher levels in the prostate, colon, and intestinal tissues relative to the other organs studied. Importantly, the predilection of bioactive pomegranate ellagitannins metabolites to localize in prostate tissue, combined with clinical data demonstrating the anticancer effects of pomegranate juice, suggests the potential for pomegranate products to play a role in prostate cancer chemoprevention. Whether uro-lithins in human prostate tissue can be used as a biomarker following the long-term administration of pomegranate juice or pomegranate extract remains to be determined. /pomegranate extract/

来源:Hazardous Substances Data Bank (HSDB)

代谢

本研究评估了在Sprague-DAwley大鼠中，连续37天口服含有6%石榴醇的饮食可能产生的毒性效应。通过高效液相色谱-二极管阵列检测-串联质谱（HPLC-DAD-MS-MS）在血浆、肝脏和肾脏中鉴定了石榴醇及其相关代谢物。在肝脏和肾脏中检测到了五种与石榴醇相关的代谢物，即两种鞣花酸衍生物、石榴酸、3,8-二羟基-6H-二苯并[b,d]吡喃-6-酮葡萄糖醛酸苷和3,8,10-三羟基-6H-二苯并[b,d]吡喃-6-酮。

... The present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one.

来源:Hazardous Substances Data Bank (HSDB)

代谢

几种果汁据报道会导致食物-药物相互作用，主要是影响细胞色素P450活性；然而，对于果汁对结合反应的影响知之甚少。在测试的几种果汁（苹果、桃子、橙子、菠萝、葡萄柚和石榴）中，石榴汁在Caco-2细胞中强烈抑制了1-萘酚的硫酸结合。这种抑制作用与剂量和培养时间有关，半抑制浓度（IC50）值为2.7%（体积比）。相比之下，所检测的任何果汁在Caco-2细胞中对1-萘酚的葡萄糖醛酸化没有明显的抑制作用。石榴汁中最丰富的抗氧化多酚安石榴苷也被发现能强烈抑制Caco-2细胞中的硫酸结合，IC50为45微摩尔，与石榴汁的一致。这些数据表明，安石榴苷是石榴汁抑制硫酸结合的主要责任物质。作者还证明，石榴汁和安石榴苷都能在体外以与Caco-2细胞中使用的浓度几乎相等的浓度抑制Caco-2细胞中的酚磺基转移酶活性。然而，石榴汁对Caco-2细胞中的磺基转移酶SULT1A家族基因（SULT1A1和SULT1A3）的表达没有影响。这些结果表明，安石榴苷在Caco-2细胞中抑制磺基转移酶活性是1-萘基硫酸积累减少的原因。数据还表明，石榴汁中的成分，很可能是安石榴苷，损害了硫酸结合的肠道功能，这可能会影响药物和食物以及环境中存在的其他化合物的生物利用度。这些效果可能与石榴汁的抗致癌性质有关。

Several fruit juices have been reported to cause food-drug interactions, mainly affecting cytochrome P450 activity; however, little is known about the effects of fruit juices on conjugation reactions. Among several fruit juices tested (apple, peach, orange, pineapple, grapefruit, and pomegranate), pomegranate juice potently inhibited the sulfoconjugation of 1-naphthol in Caco-2 cells. This inhibition was both dose- and culture time-dependent, with a 50% inhibitory concentration (IC(50)) value calculated at 2.7% (vol/vol). In contrast, no obvious inhibition of glucuronidation of 1-naphthol in Caco-2 cells was observed by any of the juices examined. Punicalagin, the most abundant antioxidant polyphenol in pomegranate juice, was also found to strongly inhibit sulfoconjugation in Caco-2 cells with an IC(50) of 45 uM, which is consistent with that of pomegranate juice. These data suggest that punicalagin is mainly responsible for the inhibition of sulfoconjugation by pomegranate juice. /The authors/ additionally demonstrated that pomegranate juice and punicalagin both inhibit phenol sulfotransferase activity in Caco-2 cells in vitro, at concentrations that are almost equivalent to those used in the Caco-2 cells. Pomegranate juice, however, shows no effects on the expression of the sulfotransferase SULT1A family of genes (SULT1A1 and SULT1A3) in Caco-2 cells. These results indicate that the inhibition of sulfotransferase activity by punicalagin in Caco-2 cells is responsible for the reductions seen in 1-naphthyl sulfate accumulation. /The/ data also suggest that constituents of pomegranate juice, most probably punicala