salvianolic acid B | 115939-25-8

• 物质功能分类: 生物化工 - 提取物
• 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: salvianolic acid B
• 英文别名: 4-[(1E)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]-3-oxo-1-propen-1-yl]-2-(3,4-dihydroxyphenyl)-2,3-dihydro-7-hydroxy-3-benzofurancarboxylic acid (2S,3S)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethyl] ester；monardic acid B；lithospermic acid B；salvianolic acid-B；SAB；(R)-2-(((2R,3R)-4-((E)-3-((R)-1-Carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-en-1-yl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyl)oxy)-3-(3,4-dihydroxyphenyl)propanoic acid；(2R)-2-[(E)-3-[(2R,3R)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyl]oxy-3-(3,4-dihydroxyphenyl)propanoic acid
• CAS: 115939-25-8
• 化学式: C₃₆H₃₀O₁₆
• 分子量: 718.625
• InChiKey: SNKFFCBZYFGCQN-PDVBOLEISA-N

物化性质

• 熔点：
  >149oC (dec.)
• 溶解度：
  DMSO（微溶）、乙醇（微溶）、甲醇（微溶）
• LogP：
  2.140 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  278
• 氢给体数：
  9
• 氢受体数：
  16

安全信息

• WGK Germany：
  3
• 储存条件：
  | 室温 |

制备方法与用途

概述

心血管疾病是一种严重威胁人类健康的疾病，其特点是发病率高、致残率高、死亡率高，目前已成为导致人类死亡的首要原因。因此，寻找能够有效治疗心血管病的药物成为了临床面临的首要问题。传统的活血化瘀中药丹参因其具有祛瘀止痛、活血通经的功效，广泛用于心血管疾病的治疗。研究表明，丹酚酸（salvianolic acids）是丹参中含量最丰富的水溶性物质，而其中丹酚酸B则是生物活性最强的化合物。

研究发现，丹酚酸不仅对心肌缺血/再灌注损伤具有保护作用，还对心肌梗死及心肌细胞肥大均有保护作用。

药理作用 保护心脏的作用

• 对心肌梗死的保护：采用冠状动脉结扎方法构建大鼠心肌梗死模型（myocardial infarction, MI），考察丹酚酸B对MI的心脏保护作用。结果显示，与对照组相比，丹酚酸B能够显著发挥心脏保护作用。
• 机制研究：主要通过抑制瘦素和内皮素-活性氧簇(ET-ROS)的上调，并恢复心肌中心肌细胞肌浆网钙ATP酶2a(sarco/endoplasmic reticulum ATPase 2a, SERCA2a)和受磷蛋白的正常表达，发挥保护心脏的作用。

抑制心肌肥大

• 抑制AngⅡ诱导的心肌细胞肥大：考察丹酚酸B对血管紧张素Ⅱ(angiotensin II, AngⅡ)诱导的新生大鼠心肌细胞肥大的影响。结果显示，丹酚酸B能够显著抑制AngⅡ诱导的心肌细胞的肥大。
• 机制研究：发现心钠素和脑钠素mRNA表达下降及细胞表面积减少。进一步研究表明，丹酚酸B能够抑制聚腺苷二磷酸核糖聚合酶1(poly(ADP-ribose)polymerase-1, PARP-1)的活性；过表达PARP-1会减弱丹酚酸B对心肌细胞肥大的保护作用。

化学性质

• 类白色结晶粉末，可溶于水、乙醇和甲醇。
• 来源于丹参根茎。

用途

• 具有抗氧化、保护心脏、保护脑及抗肿瘤的作用。

反应信息

• 作为反应物：
  描述：

  salvianolic acid B 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (2R)-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (R)-PGME amide
  参考文献：
  名称：

  Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa and Lithospermum erythrorhizon

  摘要：

  Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (75,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.fitote.2013.08.009

文献信息

• Salvianolic acid B suppresses hepatic fibrosis by inhibiting ceramide glucosyltransferase in hepatic stellate cells
  作者：Zi-bo Li、Lin Jiang、Jia-dong Ni、Yuan-hang Xu、Fang Liu、Wen-ming Liu、Shao-gui Wang、Zhong-qiu Liu、Cai-yan Wang

  DOI：10.1038/s41401-022-01044-9

  日期：——

  UDP-glucose ceramide glucosyltransferase (UGCG) is the first key enzyme in glycosphingolipid (GSL) metabolism that produces glucosylceramide (GlcCer). Increased UGCG synthesis is associated with cell proliferation, invasion and multidrug resistance in human cancers. In this study we investigated the role of UGCG in the pathogenesis of hepatic fibrosis. We first found that UGCG was over-expressed in fibrotic livers and activated hepatic stellate cells (HSCs). In human HSC-LX2 cells, inhibition of UGCG with PDMP or knockdown of UGCG suppressed the expression of the biomarkers of HSC activation (α-SMA and collagen I). Furthermore, pretreatment with PDMP (40 μM) impaired lysosomal homeostasis and blocked the process of autophagy, leading to activation of retinoic acid signaling pathway and accumulation of lipid droplets. After exploring the structure and key catalytic residues of UGCG in the activation of HSCs, we conducted virtual screening, molecular interaction and molecular docking experiments, and demonstrated salvianolic acid B (SAB) from the traditional Chinese medicine Salvia miltiorrhiza as an UGCG inhibitor with an IC50 value of 159 μM. In CCl4-induced mouse liver fibrosis, intraperitoneal administration of SAB (30 mg · kg−1 · d−1, for 4 weeks) significantly alleviated hepatic fibrogenesis by inhibiting the activation of HSCs and collagen deposition. In addition, SAB displayed better anti-inflammatory effects in CCl4-induced liver fibrosis. These results suggest that UGCG may represent a therapeutic target for liver fibrosis; SAB could act as an inhibitor of UGCG, which is expected to be a candidate drug for the treatment of liver fibrosis.

  UDP-葡萄糖神经酰胺葡萄糖基转移酶（UGCG）是糖磷脂（GSL）代谢过程中产生葡萄糖基甘油酰胺（GlcCer）的第一个关键酶。UGCG 合成的增加与人类癌症的细胞增殖、侵袭和多药耐药性有关。在这项研究中，我们探讨了 UGCG 在肝纤维化发病机制中的作用。我们首先发现，UGCG 在纤维化肝脏和活化的肝星状细胞（HSCs）中过度表达。在人 HSC-LX2 细胞中，用 PDMP 抑制 UGCG 或敲除 UGCG 可抑制 HSC 活化生物标志物（δ-SMA 和胶原 I）的表达。此外，PDMP（40μM）还会破坏溶酶体的稳态，阻断自噬过程，导致维甲酸信号通路的激活和脂滴的积累。在探索了UGCG在激活造血干细胞过程中的结构和关键催化残基后，我们进行了虚拟筛选、分子相互作用和分子对接实验，证明中药丹参中的丹参酚酸B（SAB）是一种UGCG抑制剂，其IC50值为159δ¼M。此外，SAB对CCl4诱导的肝纤维化具有更好的抗炎作用。这些结果表明，UGCG可能是肝纤维化的治疗靶点；SAB可作为UGCG的抑制剂，有望成为治疗肝纤维化的候选药物。
• Improving the NQO1-Inducing Activities of Phenolic Acids from Radix Salvia miltiorrhiza: a Methylation Strategy
  作者：Xiaoyu Zhang、Zhihang Song、Jinzhong Xu、Zhongjun Ma

  DOI：10.1111/j.1747-0285.2011.01171.x

  日期：2011.10

  NAD(P)H: quinone oxidoreductase1 (NQO1) is an important detoxification enzyme that can protect mammalian cells against toxic quinones and reduce the risk of tumorigenesis. In this study, it was found that salvianolic acid B (SaB), lithospermic acid (LA), and rosmarinic acid (RA), three main hydrophilic constituents in Danshen, conjugated with glutathione (GSH) easily in vitro but exhibited no NQO1‐inducing activities in Hepa 1c1c7 cells, which might attribute to their poor absorptions. After a simple methylation strategy that aimed at improving the liposolubility, both the NQO1‐inducing activities and the absorptions in cells of the phenolic acids improved obviously, without losing the GSH‐conjugating abilities. The concentration to double the specific activity of NQ01 values of methylated products of lithospermic acid and rosmarinic acid were 17.86 ± 2.34 μg/mL and 11.97 ± 0.60 μg/mL, respectively. The findings indicated that methylation is an effective strategy to improve the NQO1‐inducing activities of phenolic acids in Danshen.
• Reassignment of the Configuration of Salvianolic Acid B and Establishment of Its Identity with Lithospermic Acid B
  作者：Anja Watzke、Steven J. O'Malley、Robert G. Bergman、Jonathan A. Ellman

  DOI：10.1021/np060136w

  日期：2006.8.1

  Salvianolic acid B and lithospermic acid B are the major components of Salvia miltiorrhiza, which is one of the most popular herbal traditional medicines in Asian countries. Salvianolic acid B and lithospermic acid B are reported to have identical structures except for the configurational assignments of two stereocenters. Through chemical correlation between a degradation product of salvianolic acid B and synthetic material, the absolute configuration of salvianolic acid B has been corrected to establish that salvianolic acid B and lithospermic acid B are in fact the same compound.
• AI, CHUN-BO;LI, LIAN-NIANG, J. NATUR. PROD., 51,(1988) N 1, 145-149
  作者：AI, CHUN-BO、LI, LIAN-NIANG

  DOI：——

  日期：——
• Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa and Lithospermum erythrorhizon
  作者：Toshihiro Murata、Kanae Oyama、Minami Fujiyama、Bunmei Oobayashi、Kaoru Umehara、Toshio Miyase、Fumihiko Yoshizaki

  DOI：10.1016/j.fitote.2013.08.009

  日期：2013.12

  Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (75,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities. (C) 2013 Elsevier B.V. All rights reserved.