山奈酚 | 520-18-3

• 物质功能分类: 天然产物 - 黄酮类化合物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 山奈酚
• 中文别名: 山柰素；山柰黄酮醇；3,4',5,7-四羟基黄酮水合物；山柰酚-3；四羟基黄酮；百蕊草素Ⅲ；山奈酚水合物；山柰酚
• 英文名称: kaempferol
• 英文别名: 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one；kaempherol；3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one；kaemferol；3,4',5,7-tetrahydroxyflavone；3,4′,5,7-tetrahydroxyflavone；3,5,7‑trihydroxy‑2‑(4‑hydroxyphenyl)‑4H‑1‑benzopyran‑4‑one；4′,5,7-trihydroxyflavonol；3,5,7,4'-tetrahydroxyflavone；3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one
• CAS: 520-18-3
• 化学式: C₁₅H₁₀O₆
• mdl: MFCD00016938
• 分子量: 286.241
• InChiKey: IYRMWMYZSQPJKC-UHFFFAOYSA-N

物化性质

• 熔点：
  276°C
• 沸点：
  348.61°C (rough estimate)
• 密度：
  1.2981 (rough estimate)
• 溶解度：
  乙醇：20 mg/mL
• LogP：
  2.685 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Yellow needles from alcohol and water
• 蒸汽压力：
  1.1X10-13mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits acrid smoke and fumes.
• 碰撞截面：
  162.9 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]
• 稳定性/保质期：

  1. 又称山奈黄素、山奈黄酮醇、山奈素、四羟基黄酮、莰非醇、猫眼草素I和百蕊草素III，是一种黄酮类化合物。它以黄色针状结晶的形式存在。与三氯化铁试液反应呈绿色，并可还原费林试剂及氨制硝酸银溶液。本品是木贼科植物的特征性成分，还存在于姜科植物山奈（Kaempferia galangal L.）和小檗科植物窝儿七（Diphylleia sinensis Li.）的根茎以及大戟科植物猫眼草（Euphorbia lunulata Bge.）的地上部分。

  2. 它还存在于烟叶中。

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

代谢

为了阐明毛地黄素在大肠中的代谢，研究了猪盲肠微生物对其的生物转化。此外，还研究了猪盲肠微生物降解高良姜素（3,5,7-三羟基黄酮）、山奈酚（3,5,7,4'-四羟基黄酮）、芹菜素（5,7,4'-三羟基黄酮）和木犀草素（5,7,3',4'-四羟基黄酮）的效率。通过高效液相色谱（HPLC）-二极管阵列检测、HPLC-电喷雾离子化-串联质谱和高效液相色谱-质谱对形成的代谢物进行了鉴定。盲肠微生物将...山奈酚转化为4-羟基苯乙酸、间苯三酚和4-甲基苯酚；...为了阐明B环上不同羟基化模式对黄酮类化合物降解程度的影响，将高良姜素和山奈酚的转化以及芹菜素和木犀草素的转化分别与槲皮素（3,5,7,3',4'-五羟基黄酮）和黄烷素（5.7-二羟基黄酮）进行了比较。无论黄酮类化合物的亚类如何，B环上4'位置的羟基似乎是对快速分解的必要条件。B环上额外的羟基并不会影响降解程度。

To elucidate the metabolism of hispidulin in the large intestine, its biotransformation by the pig caecal microflora was studied. In addition, the efficiency of the pig caecal microflora to degrade galangin (3,5,7-trihydroxyflavone), kaempferol (3,5,7,4?-tetrahydroxyflavone), apigenin (5,7,4?-trihydroxyflavone), and luteolin (5,7,3?,4?- tetrahydroxyflavone) was investigated. Identification of the formed metabolites was performed by high-performance liquid chromatography (HPLC)-diode array detection, HPLC-electrospray ionization-tandem mass spectrometry, and high-resolution gas chromatography-mass spectrometry. The caecal microflora transformed ... kaempferol to 4-hydroxyphenylacetic acid, phloroglucinol, and 4-methylphenol; ... To elucidate to what extent different hydroxylation patterns on the B-ring influence the degradation degree of flavonoids, the conversions of galangin and kaempferol as well as that of apigenin and luteolin were compared with those of quercetin (3,5,7,3?, 4?-pentahydroxyflavone) and chrysin (5.7-dihydroxyflavone), respectively. Regardless of the flavonoid subclass, the presence of a hydroxy group at the 4?-position seems to be a prerequisite for fast breakdown. An additional hydroxy group at the B-ring did not affect the degradation degree.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大鼠肝细胞对黄酮醇类化合物槲皮素和山奈酚的代谢进行了研究，使用液相色谱与电喷雾质谱联用（LC-ESI MS）技术。槲皮素和山奈酚被广泛代谢（槲皮素98.8 +/- 0.1%，山奈酚81.0 +/- 5.1%，n = 4），在培养后检测到槲皮素的四种葡萄糖苷酸和山奈酚的两种葡萄糖苷酸。与大鼠肝细胞共同培养后形成的槲皮素和山奈酚的葡萄糖苷酸被鉴定为与UDP-葡萄糖苷酸转移酶同型UGT1A9培养后形成的相同物质。此外，分析了服用富含黄酮糖苷的银杏胶囊后的人类志愿者的血浆样本，通过LC-MS检测黄酮糖苷酸和黄酮糖苷的存在。报告了血浆样本中存在黄酮糖苷的证据。结果表明，UGT1A9是代谢黄酮的关键UDP-葡萄糖苷酸转移酶同型，且完整黄酮糖苷的吸收是可能的。

The metabolism of the flavonoids quercetin and kaempferol by rat hepatocytes was investigated using liquid chromatography coupled with electrospray mass spectrometry (LC-ESI MS). Quercetin and kaempferol were extensively metabolized (98.8 +/- 0.1% and 81.0 +/- 5.1% respectively, n = 4), with four glucuronides of quercetin and two of kaempferol being detected after incubation. The glucuronides of quercetin and kaempferol formed upon incubation with rat hepatocytes were identified as the same ones formed after incubation with the UDP-glucuronosyltransferase isoform UGT1A9. In addition, plasma samples from human volunteers taken after consumption of capsules of Ginkgo biloba, a plant rich in flavonoid glycosides, were analysed by LC-MS for the presence of flavonoid glucuronides and flavonoid glycosides. Reported is evidence for the presence of flavonoid glycosides in samples of plasma. The results suggest that UGT1A9 is a key UDP-glucuronosyltransferase isoform for the metabolism of flavonoids, and that absorption of intact flavonoid glycosides is possible.

来源:Hazardous Substances Data Bank (HSDB)

代谢

槲皮素是一种在可食用植物中广泛分布的黄烷醇，它已被证明在缺乏外部代谢系统的条件下对V79细胞具有基因毒性。外部代谢系统的存在，如大鼠肝脏匀浆（S9混合物），会导致其基因毒性增加，这归因于它通过细胞色素P450（CYP）单加氧酶系统转化为更具基因毒性的黄烷醇槲皮素。

Kaempferol is a flavonoid widely distributed in edible plants and has been shown to be genotoxic to V79 cells in the absence of external metabolizing systems. The presence of an external metabolizing system, such as rat liver homogenates (S9 mix), leads to an increase in its genotoxicity, which is attributed to its biotransformation to the more genotoxic flavonoid quercetin, via the cytochrome P450 (CYP) mono-oxygenase system. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

槲皮素已知的人类代谢物包括(2S,3S,4S,5R)-6-[3,5-二羟基-2-(4-羟基苯基)-4-氧杂色酮-7-基]氧基-3,4,5-三羟基氧杂环己烷-2-羧酸和槲皮素-3-葡萄糖苷酸。

Kaempferol has known human metabolites that include (2S,3S,4S,5R)-6-[3,5-Dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid and Kaempferol-3-glucuronide.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌物分类

国际癌症研究机构致癌物：山柰酚

IARC Carcinogenic Agent:Kaempferol

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第31卷：（1983年）某些食品添加剂、饲料添加剂和天然存在物质

IARC Monographs:Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

3, 其对人类致癌性无法分类。

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

据报道，他莫昔芬是P-糖蛋白（P-gp）和微粒体细胞色素P450（CYP）3A的底物，而山奈酚是P-gp和CYP3A的抑制剂。因此，可以预期山奈酚会影响他莫昔芬的药代动力学。于是，在没有或伴随口服山奈酚（2.5和10 mg/kg）的情况下，口服给予他莫昔芬（10 mg/kg）。在山奈酚的存在下，他莫昔芬从时间零到无穷大的血浆浓度-时间曲线下的总面积（AUC）显著增加，C(max)显著较高，F比没有山奈酚时大得多。口服山奈酚增强了他莫昔芬的口服生物利用度，这可能是由于山奈酚抑制了CYP3A和P-gp。山奈酚的存在并未改变他莫昔芬代谢物4-羟基他莫昔芬的药代动力学参数。这可能是因为在老鼠体内，CYP3A对4-羟基他莫昔芬形成的贡献并不显著。

It has been reported that tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A, and kaempferol is an inhibitor of P-gp and CYP3A. Hence, it could be expected that kaempferol would affect the pharmacokinetics of tamoxifen. Thus, tamoxifen was administered orally (10 mg/kg) without or with oral kaempferol (2.5 and 10 mg/kg). In the presence of kaempferol, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of tamoxifen was significantly greater, C(max) was significantly higher and F was considerably greater than those without kaempferol. The enhanced bioavailability of oral tamoxifen by oral kaempferol could have been due to an inhibition of CYP3A and P-gp by kaempferol. The presence of kaempferol did not alter the pharmacokinetic parameters of a metabolite of tamoxifen, 4-hydroxytamoxifen. This could have been because the contribution of CYP3A to the formation of 4-hydroxytamoxifen is not considerable in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这项研究旨在评估在健康人类中，通过监测摄入量与排泄量的关系，在食用豆类（Phaseolus vulgaris L.）后，槲皮素的生物利用率。在七名从煮熟的豆类中摄取槲皮素的健康的受试者中，水解黄酮醇的最大排泄量在摄入后2-8小时获得。发现男性和女性受试者之间尿排泄的性别差异分别为槲皮素剂量的6.10+/-5.50%和5.40+/-5.40%。尽管在最高和最低排泄浓度之间发现了6.72倍的人际差异，但所有个体都表现出相似的排泄轮廓。此外，志愿者槲皮素排泄百分比与体重指数之间存在直接相关性，相关指数等于0.80。除两名个体外，所有个体在摄入后2小时都表现出槲皮素排泄的第一个高峰。该研究揭示了在槲皮素摄入后个体间排泄能力的信息，并表明槲皮素可以用作黄酮醇摄入的生物标志物。

The aim of this study was to assess kaempferol bioavailability in healthy humans, after bean (Phaseolus vulgaris L.) consumption through the monitoring of the excretion in relation to intake. In seven healthy subjects receiving kaempferol from cooked bean, maximum excretion of hydrolyzed flavonol was obtained after 2-8 hr. Intersexual variations in urinary excretion were found to be 6.10+/-5.50% and 5.40+/-5.40% of the kaempferol dose for male and female subjects, respectively. Although a 6.72-fold inter-individual variation between the highest and lowest excretion concentrations was found, all individuals exhibited similar excretion profiles. Moreover, a direct correlation between the percentage of kaempferol excreted and the body mass index of volunteers was observed with a correlation index equal to 0.80. All except two individuals exhibited a first peak of kaempferol excretion 2 hr after ingestion. The study reveals information about inter-individual excretion capacity after kaempferol intake and that kaempferol can be used as a biomarker for flavonol consumption.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...对菊苣中的山奈酚进行药代动力学研究.../在/四名健康男性和四名健康女性中进行了研究。山奈酚从一个相对较低的剂量（9毫克）开始，从菊苣中被吸收，平均最大血浆浓度为0.1微摩尔，在5.8小时时，表明从小肠远端和/或结肠吸收。尽管在最高和最低最大血浆浓度之间观察到了7.5倍个体间差异，但大多数个体的药代动力学特征表现出显著的一致性。这与主要在大肠吸收的其他黄酮类化合物（例如芸香苷）的概况形成对比。在24小时内，平均有1.9%的山奈酚剂量被排泄。大多数受试者还显示了一个早期的吸收峰，可能是对应于在菊苣中以14%水平存在的山奈酚-3-葡萄糖苷。山奈酚-3-葡萄糖醛酸苷是在血浆和尿液中检测到的主要化合物。槲皮素在血浆或尿液中未被检测到，表明山奈酚缺乏I相羟基化。即使在低口服剂量下，山奈酚在人体中的吸收效率也高于槲皮素。血浆中的主要形式是3-葡萄糖醛酸苷，吸收和排泄的个体间差异较低，这表明尿中山奈酚可以作为暴露的生物标志物。

... A pharmacokinetic study of kaempferol from endive ... /was studied in / four healthy males and four healthy females. Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 uM, at a time of 5.8 hr, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 hr. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

十名平均年龄为28岁的成年志愿者一次性口服给予了六片银杏叶提取物。通过反相高效液相色谱法（RP-HPLC）测定了人尿液中不同时期的槲皮素和山奈酚。结果显示，槲皮素的消除速率常数k和吸收速率常数ka略高于山奈酚；槲皮素的吸收半衰期（t(1/2a)）、消除半衰期（t(1/2)）和达峰时间（t(max)）均低于山奈酚，但差异无统计学意义。槲皮素和山奈酚的平均ka值分别为0.61 hr(-1)和0.55 hr(-1)，t(1/2a)为1.51 hr和1.56 hr，k为0.37 hr(-1)和0.30 hr(-1)，t(1/2)为2.17 hr和2.76 hr，T(max)为2.30 hr和2.68 hr，这意味着槲皮素和山奈酚的吸收和消除分别为0.17%和0.22%。槲皮素和山奈酚主要以葡萄糖苷酸形式从人体尿液中排出。

Ten adult volunteers with an average age 28 years were given a single oral dose of six tablets of Ginkgo biloba extract. Quercetin and kaempferol in different period of human urine were determined by using RP-HPLC. The results showed the elimination rate constant k and the absorption rate constant ka of quercetin were slightly more than that of kaempferol; and the absorption half-life (t(1/2a)), the elimination half-life (t(1/2)) and t(max) of quercetin were less than that of kaempferol, the differences were, however, not statistically significant. The mean values of ka were 0.61 hr(-1) and 0.55 hr(-1), t(1/2a) 1.51 hr and 1.56 hr, k 0.37 hr(-1) and 0.30 hr(-1), t(1/2) 2.17 hr and 2.76 hr, T(max) 2.30 hr and 2.68 hr for quercetin and kaempferol, respectively, which mean absorption and elimination of quercetin and kaempferol are 0.17% and 0.22%, respectively. Quercetin and kaempferol are excreted in the human urine mainly as glucuronides.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

本研究的目标是调查槲皮素和山奈酚是否能够被转运进入原代培养的脑神经元，建立一个实用的HPLC-UV检测方法用于测定神经元中的这两种黄酮醇，并研究它们通过神经元的摄取和传输行为。目前的结果显示，在高浓度10微克/毫升条件下，随着培养时间的延长，神经元中山奈酚的水平呈线性增加然后达到平台期，但在另外两个浓度1微克/毫升和0.1微克/毫升下并未出现此现象。然而，在三个培养浓度下均未检测到神经元中的槲皮素水平，且在细胞中出现了一个新的峰，其保留时间（3.42分钟）比槲皮素（4.65分钟）短。这一现象表明槲皮素可能被转运进入神经元并迅速代谢为某些衍生物。当神经元与含有高剂量山奈酚的培养液一起培养时，山奈酚可以以浓度和时间依赖性的方式被转运进入神经元。培养基中山奈酚的浓度与细胞中山奈酚的浓度之间存在明显相关性，表明随着剂量的增加（10微克/毫升），细胞中山奈酚的摄取也增加。然而，培养基中槲皮素的浓度与细胞中槲皮素的浓度之间存在负相关。结果表明，山奈酚和槲皮素被神经元以不同的方式处理，这可能是它们对原代培养皮层细胞产生不同效果的一个重要因素。

The objective of this study was to investigate whether kaempferol and quercetin could be transported into primary cultured cerebral neurons, to establish a practical HPLC method with UV detection for the two flavonols in the neurons, and to study the uptake and transport behaviors of them through the neurons. The present results showed that the level of kaempferol in the neurons increased linearly and then reached a plateau with incubation time at the high concentration of 10 ?g/mL, but not at the other two concentrations of 1 and 0.1 ug/mL. However, the levels of quercetin in the neurons were not detected at the three incubating concentrations, and there was a new peak detected in the cell whose retention time was shorter (3.42 min) than that of quercetin (4.65 min). This phenomenon suggested that quercetin might be transported into the neurons and then metabolized quickly to some derivative. Kaempferol could be transported into the neurons in a concentration- and time-dependent manner when the neurons were incubated with the culture medium containing kaempferol at the high dose. There was an apparent correlation between the concentrations of kaempferol in the medium and in the cell, indicating that the uptake of kaempferol in the cell increased along with its dose (10 ug/mL). However, there was a negative correlation between the concentrations of quercetin in the medium and in the cell. The results suggested that kaempferol and quercetin were disposed by the neurons at different way, and this might be an important factor for their different effects on primary cultured cortical cells.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3,-
• 海关编码：
  2914501900
• 危险品运输编号：
  UN 2811 6.1 / PGIII
• RTECS号：
  LK9275200
• 危险标志：
  GHS06,GHS08
• 危险性描述：
  H301,H341
• 危险性防范说明：
  P281,P301 + P310
• 包装等级：
  III
• 危险类别：
  6.1
• 储存条件：
  储存于阴凉、干燥、通风良好的库房内，远离火种和热源，避免阳光直射，并确保包装密封。应将该物品与酸类及食用化学品分开存放，切忌混储。同时，在储区备有合适的材料以收容可能的泄漏物。

SDS

山奈酚水合物 修改号码：6

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模块 1. 化学品
产品名称： Kaempferol Hydrate
修改号码： 6

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模块 2. 危险性概述
GHS分类
物理性危害 未分类
健康危害 未分类
环境危害 未分类
GHS标签元素
图标或危害标志 无
信号词 无信号词
危险描述 无
防范说明 无

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模块 3. 成分/组成信息
单一物质/混和物 单一物质
化学名(中文名)： 山奈酚水合物
百分比： >97.0%(HPLC)
CAS编码： 520-18-3
俗名： 3,4',5,7-Tetrahydroxyflavone Hydrate
分子式：
C15H10O6·xH2O

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模块 4. 急救措施
吸入： 将受害者移到新鲜空气处，保持呼吸通畅，休息。若感不适请求医/就诊。
皮肤接触： 立即去除/脱掉所有被污染的衣物。用水清洗皮肤/淋浴。
若皮肤刺激或发生皮疹：求医/就诊。
眼睛接触： 用水小心清洗几分钟。如果方便，易操作，摘除隐形眼镜。继续清洗。
如果眼睛刺激：求医/就诊。
食入： 若感不适，求医/就诊。漱口。
紧急救助者的防护： 救援者需要穿戴个人防护用品，比如橡胶手套和气密性护目镜。

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模块 5. 消防措施
合适的灭火剂： 干粉，泡沫，雾状水，二氧化碳
山奈酚水合物 修改号码：6

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模块 5. 消防措施
特定方法： 从上风处灭火，根据周围环境选择合适的灭火方法。
非相关人员应该撤离至安全地方。
周围一旦着火：如果安全，移去可移动容器。
消防员的特殊防护用具： 灭火时，一定要穿戴个人防护用品。

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模块 6. 泄漏应急处理
个人防护措施，防护用具， 使用个人防护用品�