羟基芍药苷 | 39011-91-1

• 物质功能分类: 生物化工 - 提取物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 羟基芍药苷
• 中文别名: 氧化芍药苷
• 英文名称: Oxypaeoniflora
• 英文别名: [(1R,2S,3R,5R,6R,8S)-6-hydroxy-8-methyl-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9,10-dioxatetracyclo[4.3.1.02,5.03,8]decan-2-yl]methyl 4-hydroxybenzoate
• CAS: 39011-91-1
• 化学式: C₂₃H₂₈O₁₂
• 分子量: 496.5
• InChiKey: FCHVXNVDFYXLIL-WRJNSLSBSA-N

物化性质

• 熔点：
  >162°C (dec.)
• 沸点：
  737.1±60.0 °C(Predicted)
• 密度：
  1.71±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  185
• 氢给体数：
  6
• 氢受体数：
  12

安全信息

• WGK Germany：
  3

制备方法与用途

应用

氧化芍药苷细胞毒性实验得知，其半数细胞毒性浓度（CC50）为250.0μg/ml。质量浓度200.0μg/ml以下无细胞毒性，且200.0μg/ml的氧化芍药苷对泡沫细胞胆固醇流出有明显促进作用。选取200.0μg/ml作为实验浓度。与apoA-1组相比，氧化芍药苷处理组的胆固醇流出率增加了26%，这提示氧化芍药苷能够促进泡沫细胞内胆固醇的流出。

进一步采用激光共聚焦显微镜观察氧化芍药苷处理的泡沫细胞内ADFP（一种脂肪分化相关蛋白）的表达变化。ADFP是apoA-1介导的胆固醇流出通路中的转运囊泡的组成部分，也是THP-1巨噬细胞脂质沉积和动脉粥样硬化病变的标志性物质。共聚焦显微镜观察到ac-LDL泡沫细胞组有大量ADFP红色荧光蛋白表达，并且在整个细胞内呈点状分布；apoA-1组及氧化芍药苷处理组的红色荧光强度逐渐减弱，且多集中于细胞膜边缘位置。同时，采用Western blot方法分析泡沫细胞内ADFP的表达变化，结果显示氧化芍药苷处理后ADFP的表达量较apoA-1组下降28%。这些结果提示，氧化芍药苷具有促进泡沫细胞胆固醇流出的作用。

此外，芍药苷类化合物包括氧化芍药苷在制备治疗脓毒症药物中具有应用价值。

生物活性

Oxypaeoniflorin是一种抗氧化剂，是从牡丹科植物中分离得到的单萜糖苷化合物。它具有神经保护和抗炎作用。

体外研究

Oxypaeoniflorin (OPA; 0.1-10 μM, 8小时)明显逆转了缺氧/再氧化(H/R)-诱导的心肌细胞活性下降及凋亡增加。通过激活Sirt1/Foxo1信号通路，OPA抑制心肌组织和H9c2细胞的凋亡。

Oxypaeoniflorin (0-30 μM)通过调控TLR、ERK和p38 MAP激酶信号传导途径，在脂多糖(LPS)刺激的RAW264.7细胞中减轻了炎症效应。

体内研究

Oxypaeoniflorin (OPA; 10-40 mg/kg，灌胃给药，每日一次，共30天)治疗显著减少了心脏功能紊乱，并改善了射血分数(EF)和缩短分数(FS)等指标。此外，在C57BL/6雄性小鼠（6-8周龄，20-25 g）中，OPA显著降低了与心肌梗死再灌注损伤相关的因素，如乳酸脱氢酶同工酶(CK-MB)、心脏肌钙蛋白I(cTnI)和心脏肌钙蛋白T(cTnT)的释放。

化学性质

白色结晶粉末，可溶于甲醇、乙醇、DMSO等有机溶剂。来源于牡丹皮、芍药、赤芍。

用途

羟基芍药苷具有抑制副交感神经兴奋、降低平滑肌张力和抑制其运动的作用，并可用于含量测定/鉴定/药理实验等，具有抗炎镇痛、调节免疫、治疗风湿性关节炎等作用。

文献信息

• Pharmaceutical composition containing substance inhibiting HSP47 production
  申请人：Kureha Chemical Industry Co., Ltd.

  公开号：EP0742012A2

  公开（公告）日：1996-11-13

  A pharmaceutical composition comprising a substance inhibiting HSP47 production, selected from the group consisting of a malt extract, a flavonoid compound, a protein-bound-polysaccharide obtained from a fungus belonging to Coriolus versicolor, a paeoniflorin derivative, a tocopherol derivative, and a ferulic acid derivative, and a pharmaceutically acceptable carrier is disclosed. The substance inhibiting HSP47 production can efficiently improve physiological conditions of a patient suffering from diseases exhibiting pathosis of overproduction of the extracellular matrix, and efficiently treat such diseases. Further, the substance is useful for preventing or treating various diseases accompanied with abnormal growth of the vascularization.

  本发明公开了一种药物组合物，该组合物包含一种抑制 HSP47 生成的物质，该物质选自麦芽提取物、黄酮类化合物、从属于 Coriolus versicolor 的真菌中获得的蛋白结合多糖、芍药苷衍生物、生育酚衍生物和阿魏酸衍生物组成的组，以及一种药学上可接受的载体。这种抑制 HSP47 生成的物质可以有效改善患有细胞外基质过度生成病症的患者的生理状况，并有效治疗此类疾病。此外，该物质还可用于预防或治疗伴有血管异常生长的各种疾病。
• Combination therapy for treatment of patients with neurological disorders and cerebral infarction
  申请人：Moleac Pte Ltd.

  公开号：EP2508191A1

  公开（公告）日：2012-10-10

  The present invention provides compositions and methods of treating a patient having a condition selected from the group of cerebral stroke, heart stroke, neurodegenerative diseases, brain or nervous system trauma, or neuroplasticity wherein the composition comprises: (i) at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 of: Radix Astragali (milkvetch root or Huang Qi); Rhizoma Salviae Miltiorrhizae root (red sage or Dan Shen); Radix Paeoniae Rubra (red peony or chi shao); Ligusticum Chuanxiong (Chuan Xiong); Rhizoma Notoginseng (Sanqi); Odoriferous Rosewood (Jiang Xiang); Scorpion (Quan Xie); Radix Polygalae (Yuan Zhi); Grassleaf sweetflag (Shi Changpu); Leech (Hirudo or Shuizhi); Ground beetle (Tu Bie Chong); Cow bezoar (calculus Bovis artifactus or Rengong Niuhuang); Gambirplant (ramulus uncariae cum uncis or Gou teng); and (ii) an agent used in Western medicine.

  本发明提供了治疗选自脑中风、心脏中风、神经退行性疾病、脑或神经系统创伤或神经可塑性疾病的患者的组合物和方法，其中组合物包括：(i) 至少4、5、6、7、8、9、10、11、12、13或14种：黄芪；丹参；赤芍；川芎；三七；紫檀；全蝎；蝎子（全蝎）；远志（远志）；草叶甘草（石菖蒲）；水蛭（葫芦或水芝）；地鳖虫（土鳖虫）；牛黄（牛黄结石或人参牛黄）；钩藤（钩藤或钩藤瘤）；以及 (ii) 西药中使用的制剂。
• METHOD FOR PREPARING ALBIFLORIN AND PAEONIFLORIN
  申请人：Zhang, Zuoguang

  公开号：EP2650301A1

  公开（公告）日：2013-10-16

  The present invention discloses a method for preparing high purity paeoniflorin and albiflorin simultaneously comprising: extraction of the raw material Paeonia Lactiflora by percolation or heating under reflux to obtain the Paeonia Lactiflora extract solution, then purification by macroporous absorption resin, alumina column and silica gel column in turn to obtain high purity paeoniflorin and albiflorin. The preparation method of the invention can provide high purity paeoniflorin and albiflorin with low price and energy-consumption by the identical procedure. The process is simple. The purification efficacy is high and the purification time is short.

  本发明公开了一种同时制备高纯度芍药苷和白花蛇舌草素的方法，包括：用渗漉法或回流加热法提取原料芍药，得到芍药提取液，然后依次用大孔吸收树脂、氧化铝柱和硅胶柱纯化，得到高纯度的芍药苷和白花蛇舌草素。本发明的制备方法可提供高纯度的芍药苷和白花前胡素，且价格低廉、能耗低。工艺简单。纯化效率高，纯化时间短。
• PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DIABETIC COMPLICATIONS AND ANGIOEDEMA, CONTAINING NATURAL MIXTURE EXTRACT AS ACTIVE INGREDIENT
  申请人：Korea Institute of Oriental Medicine

  公开号：EP3146976A1

  公开（公告）日：2017-03-29

  The extract of a mixture of cinnamon twig and moutan root bark, cinnamon twig and peony root, or cinnamon twig and poria according to the present invention has been confirmed to inhibit the excessive generation of advanced glycation end-products, which occurs under chronic diabetic conditions, exhibit the effect of fragmentizing a cross-link between the advanced glycation end-products and matrix proteins, have an excellent effect in inhibiting the generation of the advanced glycation end-products in a human retinal pigment epithelial cell line subjected to a hyperglycemic or aging environment, and have excellent effects in delaying, preventing, and treating diabetic complications, muscular degeneration, commotio retinae, and lower extremity edema in various animal models of diabetic complications, macular degeneration, and lower extremity edema, and thus the mixture extract can effectively be used as an active ingredient for a composition for preventing and treating diabetic complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy, and angioedema, including macular (retinal) edema, macular degeneration, and varicose veins.

  根据本发明，桂枝和牡丹根皮、桂枝和牡丹根或桂枝和茯苓的混合物提取物已被证实可抑制在慢性糖尿病条件下过度生成的高级糖化终产物、本发明具有使高级糖化终产物与基质蛋白之间的交联断裂的作用，对抑制在高血糖或老化环境下的人视网膜色素上皮细胞系中高级糖化终产物的生成有极好的效果、在各种糖尿病并发症、黄斑变性和下肢水肿动物模型中，对延缓、预防和治疗糖尿病并发症、肌肉变性、视网膜皲裂和下肢水肿具有极佳的效果、因此，该混合物提取物可有效用作预防和治疗糖尿病并发症（包括糖尿病视网膜病变、糖尿病肾病和糖尿病神经病变）和血管性水肿（包括黄斑（视网膜）水肿、黄斑变性和静脉曲张）的组合物的活性成分。
• PHARMACEUTICAL COMPOSITION FOR TREATING AND PREVENTING DEGENERATIVE NEUROLOGICAL DISORDERS, CONTAINING, AS ACTIVE INGREDIENT, MIXTURE EXTRACT OF MOUTAN ROOT BARK, ANGELICA DAHURICA ROOT AND BUPLEURUM ROOT OR FRACTION THEREOF
  申请人：University-Industry Cooperation Group of Kyung Hee University

  公开号：EP3199171A1

  公开（公告）日：2017-08-02

  The present invention relates to a pharmaceutical composition for treating and preventing degenerative neurological disorders, containing, as an active ingredient, a mixture extract of two or more types selected from the group consisting of Moutan Root Bark, Angelica Dahurica Root, and Bupleurum Root, or a fraction thereof. Specifically, the extract of the mixture of the present invention exhibits a recovery effect on mitochondrial function damage, a relieving effect on endoplasmic reticulum stress and also exhibits simultaneously an inhibitory effect on inflammatory response, which are remarkably improved compared with those exhibited in an in vitro single extract, and the extract of the mixture significantly exhibits an improvement effect on motor coordination and a protective effect on dopaminergic neurons in a Parkinson's disease animal model, and thus the extract of the mixture of the present invention or a fraction thereof can be useful as an active ingredient of a pharmaceutical composition for treating and preventing degenerative neurological disorders.

  本发明涉及一种用于治疗和预防神经系统退行性疾病的药物组合物，其有效成分包含两种或两种以上的混合提取物，这些混合提取物选自木丹根树皮、白芷根和柴胡根或其馏分组成的组。具体来说，本发明的混合物提取物对线粒体功能损伤有恢复作用，对内质网应激有缓解作用，同时对炎症反应有抑制作用，这些作用与体外单一提取物相比有明显改善、因此，本发明的混合物提取物或其馏分可用作治疗和预防退行性神经系统疾病的药物组合物的活性成分。