Magnesium lithospermate B

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: Magnesium lithospermate B
• 英文别名: MLB；Lithospermate B；magnesium;4-[(2R)-2-carboxy-2-[(E)-3-[(2S,3S)-3-[(1R)-1-carboxy-2-(3-hydroxy-4-oxidophenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyl]oxyethyl]-2-hydroxyphenolate
• 化学式: C₃₆H₂₈O₁₆*Mg
• 分子量: 740.914
• InChiKey: ANUBYMNVOPVATP-LKYMKJHQSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  0.28
• 重原子数：
  53
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  284
• 氢给体数：
  7
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  Magnesium lithospermate B 在 IR 120B resin (H⁽¹⁺⁾ form) 作用下， 生成 丹酚酸 B
  参考文献：
  名称：

  Magnesium and ammonium-potassium lithospermates B, the active principles having a uremia-preventive effect from Salvia miltiorrhiza.

  摘要：

  从丹参中分离出了对尿毒症症状有改善作用的活性成分，并将其命名为石炭酸镁（1）和石炭酸铵钾（2）。此外，还根据化学和光谱数据确定了石炭酸的立体结构，该结构一直未得到澄清。

  DOI：

  10.1248/cpb.37.340
• 作为产物：
  描述：

  丹酚酸 B 在 magnesium hydroxide 作用下， 以 水 为溶剂， 生成 Magnesium lithospermate B
  参考文献：
  名称：

  Magnesium and ammonium-potassium lithospermates B, the active principles having a uremia-preventive effect from Salvia miltiorrhiza.

  摘要：

  从丹参中分离出了对尿毒症症状有改善作用的活性成分，并将其命名为石炭酸镁（1）和石炭酸铵钾（2）。此外，还根据化学和光谱数据确定了石炭酸的立体结构，该结构一直未得到澄清。

  DOI：

  10.1248/cpb.37.340

文献信息

• Derivatives of 8-epiblechnic Acid and their Effects on Down-Regulation of Endothelin (ETA) receptor mRNA
  申请人：Chan Hardy

  公开号：US20100048618A1

  公开（公告）日：2010-02-25

  The present application discloses derivatives of 8-epiblechnic acid and use thereof in treating a disease related to endothelin receptor A or endothelin-1 (ET-1) over-expression, such as hypertension, cancer, atherosclerosis, and myocardial infarction.

  本申请公开了8-epiblechnic酸的衍生物及其在治疗与内皮素受体A或内皮素-1（ET-1）过度表达相关的疾病中的应用，例如高血压，癌症，动脉粥样硬化和心肌梗死。
• Enhancing the potency of lithospermate B for inhibiting Na+/K+-ATPase activity by forming transition metal ion complexes
  作者：Nan-Hei Lin、Tse-Yu Chung、Feng-Yin Li、Hsin-An Chen、Jason TC Tzen

  DOI：10.1038/aps.2013.32

  日期：2013.7

  To determine whether replacing Mg2+ in magnesium lithospermate B (Mg-LSB) isolated from danshen (Salvia miltiorrhiza) with other metal ions could affect its potency in inhibition of Na+/K+-ATPase activity. Eight metal ions (Na+, K+, Mg2+, Cr3+, Mn2+, Co2+, Ni2+, and Zn2+) were used to form complexes with LSB. The activity of Na+/K+-ATPase was determined by measuring the amount of inorganic phosphate (Pi) liberated from ATP. Human adrenergic neuroblastoma cell line SH-SY5Y was used to assess the intracellular Ca2+ level fluctuation and cell viability. The metal binding site on LSB and the binding mode of the metal-LSB complexes were detected by NMR and visible spectroscopy, respectively. The potencies of LSB complexed with Cr3+, Mn2+, Co2+, or Ni2+ increased by approximately 5 times compared to the naturally occurring LSB and Mg-LSB. The IC50 values of Cr-LSB, Mn-LSB, Co-LSB, Ni-LSB, LSB, and Mg-LSB in inhibition of Na+/K+-ATPase activity were 23, 17, 26, 25, 101, and 128 μmol/L, respectively. After treatment of SH-SY5Y cells with the transition metal-LSB complexes (25 μmol/L), the intracellular Ca2+ level was substantially elevated, and the cells were viable for one day. The transition metals, as exemplified by Co2+, appeared to be coordinated by two carboxylate groups and one carbonyl group of LSB. Titration of LSB against Co2+ demonstrated that the Co-LSB complex was formed with a Co2+:LSB molar ratio of 1:2 or 1:1, when [Co2+] was less than half of the [LSB] or higher than the [LSB], respectively. LSB complexed with Cr3+, Mn2+, Co2+, or Ni2+ are stable, non-toxic and more potent in inhibition of Na+/K+-ATPase. The transition metal-LSB complexes have the potential to be superior substitutes for cardiac glycosides in the treatment of congestive heart failure.

  确定用其他金属离子取代从丹参中分离的紫草酸镁 B (Mg-LSB) 中的 Mg2+ 是否会影响其抑制 Na+/K+-ATPase 活性的效力。八种金属离子（Na+、K+、Mg2+、Cr3+、Mn2+、Co2+、Ni2+ 和 Zn2+）用于与 LSB 形成络合物。 Na+/K+-ATP酶的活性通过测量ATP释放的无机磷酸盐(Pi)的量来确定。使用人肾上腺素能神经母细胞瘤细胞系 SH-SY5Y 评估细胞内 Ca2+ 水平波动和细胞活力。分别通过核磁共振和可见光谱检测LSB上的金属结合位点和金属-LSB配合物的结合模式。与天然存在的 LSB 和 Mg-LSB 相比，与 Cr3+、Mn2+、Co2+ 或 Ni2+ 复合的 LSB 的效力增加了约 5 倍。 Cr-LSB、Mn-LSB、Co-LSB、Ni-LSB、LSB 和 Mg-LSB 抑制 Na+/K+-ATPase 活性的 IC50 值为 23、17、26、25、101 和 128 μmol/分别是L。用过渡金属-LSB复合物(25μmol/L)处理SH-SY5Y细胞后，细胞内Ca2+水平显着升高，细胞可存活1天。以 Co2+ 为例的过渡金属似乎是由 LSB 的两个羧酸根基团和一个羰基配位的。 LSB 对 Co2+ 的滴定表明，当 [Co2+] 低于 [LSB] 的一半或高于 [LSB] 时，以 1:2 或 1:1 的 Co2+:LSB 摩尔比形成 Co-LSB 复合物， 分别。 LSB 与 Cr3+、Mn2+、Co2+ 或 Ni2+ 复合，稳定、无毒，并且对 Na+/K+-ATP 酶的抑制更有效。过渡金属-LSB复合物有可能成为治疗充血性心力衰竭的强心苷的优质替代品。
• 一种丹酚酸B的分离纯化方法及丹酚酸B镁盐 的制备方法
  申请人：山东大学

  公开号：CN105481809B

  公开（公告）日：2018-01-05

  本发明涉及一种丹酚酸B的分离纯化方法及丹酚酸B镁盐的制备方法，所述丹酚酸B的分离纯化方法包括以丹参或白花丹参药材为原料，经溶剂提取萃取、镁盐络合法分离纯化、MCI柱纯化、结晶与重结晶步骤。本发明采用丹酚酸B镁盐络合法，可以省去大孔吸附树脂或聚酰胺柱色谱的层析过程，纯化方法更简单和省时，成本更低。丹酚酸B镁盐的制备方法简单，成本低，而且收率高，纯度高，纯度可达98％，更适合于大生产。
• Therapeutic Effects of Lithospermate B Complexed with Mg2+ or Zn2+ on Metabolic Syndrome Induced in Rats Fed with High-Fat Diet
  作者：Sheng-Kuo Hsieh、Nan-Hei Lin、Ying-Jie Chen、Maw-Rong Lee、Wen-Ying Chen、Jason T.C. Tzen

  DOI：10.3390/molecules25040983

  日期：——

  Excessive food consumption and insufficient exercise lead to the prevalence of metabolic syndrome in modern life, which consequently increases the risk of many chronic diseases. Magnesium lithospermate B (MLB) from Danshen has been demonstrated to improve metabolic changes in high-fat diet–fed rats with metabolic syndrome. In this study, Mg2+ in MLB was successfully replaced with Zn2+ to form zinc lithospermate B (ZLB) complex. MLB (10 mg/kg /day) and ZLB of various concentrations (1, 2.5, 5, and 10 mg/kg/day) were prepared and examined for their therapeutic effects on metabolic syndrome induced in rats fed with a high-fat diet. The results showed that both MLB and ZLB were able to recover or alleviate the abnormal physiological states of high-fat diet–fed rats including weight gain, epididymal fat accumulation, fatty liver, retarded blood lipid and glucose metabolism putatively caused by insulin resistance, and elevated levels of proinflammatory cytokine, leptin, and oxidative stress. In an overall view of the animal study, the effectiveness of ZLB supplementation seemed to be better than that of MLB supplementation for the recovery of high-fat-fed rats from metabolic syndrome.

  过度饮食和不足运动导致代谢综合征在现代生活中普遍存在，从而增加了许多慢性疾病的风险。从丹参中提取的镁石斛苷B（MLB）已被证明能够改善代谢综合征高脂饮食喂养的大鼠的代谢变化。在这项研究中，成功地用锌离子取代MLB中的镁离子，形成了锌石斛苷B（ZLB）复合物。制备了MLB（每日10毫克/千克）和不同浓度（1、2.5、5和10毫克/千克/日）的ZLB，并检查它们对高脂饮食诱导的代谢综合征大鼠的治疗效果。结果表明，MLB和ZLB都能够恢复或减轻高脂饮食喂养的大鼠的异常生理状态，包括体重增加、附睾脂肪积累、脂肪肝、受阻的血脂和葡萄糖代谢（可能由胰岛素抵抗引起）以及升高的炎性细胞因子、瘦素和氧化应激水平。总体而言，动物研究表明，ZLB补充的有效性似乎比MLB补充更好，可以使高脂饮食喂养的大鼠从代谢综合征中恢复过来。
• Magnesium and ammonium-potassium lithospermates B, the active principles having a uremia-preventive effect from Salvia miltiorrhiza.
  作者：Takashi TANAKA、Satoshi MORIMOTO、Gen-ichiro NONAKA、Itsuo NISHIOKA、Takako YOKOZAWA、Hae Young CHUNG、Hikokichi OURA

  DOI：10.1248/cpb.37.340

  日期：——

  The active components which exhibit the improving effect on uremic symptoms have been isolated from Salviae miltriorrhizae Radix and characterized as magnesium lithospermate (1) and ammonium-potassium lithospermate (2). The stereostructure of lithospermic acid, which had remained unclarified, was also determined on the basis of chemical and spectroscopic data.

  从丹参中分离出了对尿毒症症状有改善作用的活性成分，并将其命名为石炭酸镁（1）和石炭酸铵钾（2）。此外，还根据化学和光谱数据确定了石炭酸的立体结构，该结构一直未得到澄清。