(1S,2R,9R,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: (1S,2R,9R,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one
• 化学式: C15H24N2O2
• 分子量: 264.36
• InChiKey: XVPBINOPNYFXID-WEFVWUPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  38.4
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 相互作用

当归（Oliv.）Diels和白芍药（Ait.）在传统中医中被广泛用于治疗炎症性疾病，如痤疮、心脏病和肝炎。阿魏酸钠（SF）和苦参碱（OMT）分别是当归（Oliv.）Diels和白芍药（Ait.）的有效成分。在本研究中，作者研究了SF和OMT联合使用的协同抗炎效果，以及它们对RAW 264.7细胞中炎症相关介质的调节作用。在体内，通过二甲苯诱导的小鼠耳肿胀模型和角叉菜胶诱导的大鼠足肿胀模型评估了SF和OMT联合使用的抗炎效果。在体外，通过实时PCR（RT-PCR）微阵列分析确定脂多糖（LPS）激活的RAW 264.7细胞中趋化因子和细胞因子的mRNA表达。通过酶联免疫吸附试验（ELISA）测量LPS刺激的RAW 264.7细胞上清液中白细胞介素-11（IL-11）、C反应蛋白（CRP）和干扰素-γ（INF-γ）的水平。SF和OMT联合使用可以显著抑制二甲苯诱导的小鼠耳肿胀和角叉菜胶诱导的大鼠足肿胀，而单独使用上述剂量的每种药物时没有发现效果。联合使用在下调LPS刺激的RAW 264.7细胞中炎症相关介质的mRNA表达方面比单独使用SF或OMT更有效。ELISA结果显示，联合使用以剂量依赖性方式协同抑制LPS诱导的IL-11、CRP和INF-γ的产生。SF和OMT联合使用显示出协同抗炎效果，其活性可能与对炎症相关介质的调节作用有关，尤其是IL-11、CRP和INF-γ。

The combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively. In this study, /the authors/ investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells. In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-gamma (INF-gamma) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA). The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-gamma production in a dose-dependent manner. The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-gamma.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

sodium ferulate (SF) 和氧化苦参碱（OMT）是从中药中提取的化合物，多年来分别在中国用于临床治疗心脏病和肝病。本研究的目的是探讨SF和OMT联合治疗的镇痛效果及其机制。通过应用乙酸扭体试验和福尔马林试验的动物疼痛模型，SF和OMT的联合使用显示出剂量依赖性的显著镇痛效果。在体外，联合治疗抑制了辣椒素在背根神经节神经元上引起的细胞内钙浓度增加。重要的是，通过全细胞膜片钳技术，证明了SF和OMT对辣椒素诱导的电流具有协同抑制效果。我们的结果提示，SF和OMT引起了显著的镇痛效果，这可能与它们对瞬时受体电位香草酸-1的协同抑制有关。

Sodium ferulate (SF) and Oxymatrine (OMT) were compounds extracted from Chinese herbs, and have been used in clinical treatment of heart and hepatic diseases, respectively, in China for many years. The objective of this study was to examine the analgesic effect and the mechanism of the combined treatment of SF and OMT. Using the animal pain models by applying Acetic Acid Writhing Test and Formalin Test, the combination of SF and OMT showed significant analgesic effect in dose-dependent manner. In vitro, the combined treatment inhibited the increase in intracellular calcium concentration evoked by capsaicin in the dorsal root ganglion neurons. Importantly, a synergistic inhibitory effect of SF and OMT on the capsaicin-induced currents was demonstrated by whole-cell patch-clamp. Our results suggest that SF and OMT cause significant analgesic effect which may be related to the synergistic inhibition of transient receptor potential vanilloid-1.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究的目的是为了探讨氧化苦参碱-黄芩苷联合物（OB）对2.2.15细胞中乙型肝炎病毒（HBV）复制以及HSC-T6细胞中α平滑肌肌动蛋白（αSMA）表达和I型胶原合成的影响。2.2.15细胞和HSC-T6细胞分别培养并给予处理。通过酶联免疫吸附试验（ELISA）检测培养上清中的HBsAg和HBeAg，并利用荧光定量PCR测定HBV DNA水平。从HSC-T6细胞中提取总RNA并逆转录成cDNA，通过PCR扩增cDNA，并以β肌动蛋白为内参表达其量。从HSC-T6细胞中提取的总细胞蛋白通过电泳分离，然后将解析的蛋白电转移至硝酸纤维素膜上。蛋白条带显现后，以β肌动蛋白为内参进行定量校正。在2.2.15细胞培养系统中，OB组对HBsAg和HBeAg分泌的抑制率显著高于氧化苦参碱组（HBsAg，P=0.043；HBeAg，P=0.026）；OB组的HBV DNA水平显著低于氧化苦参碱组（P=0.041）。在HSC-T6细胞中，OB组的αSMA mRNA和蛋白表达水平显著低于氧化苦参碱组（mRNA，P=0.013；蛋白，P=0.042）；I型胶原的mRNA和蛋白表达水平在OB组也显著低于氧化苦参碱组（mRNA，P<0.01；蛋白，P<0.01）。作者们得出结论，与氧化苦参碱相比，OB联合物在体外对2.2.15细胞中HBV复制有更好的抑制作用，并且对HSC-T6细胞中αSMA表达和I型胶原合成的抑制效果更佳。

/The aim of this was/ to study the effect of oxymatrine-baicalin combination (OB) against HBV replication in 2.2.15 cells and alpha smooth muscle actin (alpha SMA) expression, type I, collagen synthesis in HSC-T6 cells. The 2.2.15 cells and HSC-T6 cells were cultured and treated respectively. HBsAg and HBeAg in the culture supernatants were detected by ELISA and HBV DNA levels were determined by fluorescence quantitative PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNAs were amplified by PCR and the quantities were expressed in proportion to beta actin. The total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. Resolved proteins were electrophoretically transferred to nitrocellulose membrane. Protein bands were revealed and the quantities were corrected by beta actin. In the 2.2.15 cell culture system, the inhibitory rate against secretion of HBsAg and HBeAg in the OB group was significantly stronger than that in the oxymatrine group (HBsAg, P = 0.043; HBeAg, P = 0.026; respectively); HBV DNA level in the OB group was significantly lower than that in the oxymatrine group (P = 0.041). In HSC-T6 cells the mRNA and protein expression levels of alpha SMA in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P = 0.013; protein, P = 0.042; respectively); The mRNA and protein expression levels of type I collagen in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P < 0.01; protein, P < 0.01; respectively). /The authors concluded that/ OB combination has a better effect against HBV replication in 2.2.15 cells and is more effective against alpha SMA expression and type I collagen synthesis in HSC-T6 cells than oxymatrine in vitro.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苦参碱已被证实可以保护肝脏、肠道和心脏免受缺血和再灌注损伤，这种效果是通过抗炎和抗凋亡实现的。作者们因此探讨了苦参碱对大脑缺血损伤的潜在神经保护作用及其作用机制。雄性Sprague-Dawley大鼠被随机分为四组：永久性大脑中动脉闭塞（pMCAO）组、高剂量（pMCAO+苦参碱120 mg/kg）组、低剂量（pMCAO+苦参碱60 mg/kg）组和假手术组。作者们使用永久性大脑中动脉闭塞模型，在大脑缺血后立即通过腹膜内给药苦参碱，并在接下来的几天内每天给药一次。在MCAO后24小时，使用改良的六点量表评估神经缺陷；测量脑水分含量；通过免疫组化、Western印迹和RT-PCR测量NF-kappaB表达。在72小时时使用2,3,5-三苯基四氮唑（TTC）染色分析梗死体积。与pMCAO组相比，高剂量组的神经缺陷有所改善（P < 0.05），梗死体积减少（P < 0.001），脑水肿减轻（P < 0.05）。与这些指标一致，免疫组化、Western印迹和RT-PCR分析表明高剂量组的NF-kappaB表达显著降低。低剂量的苦参碱对pMCAO大鼠的NF-kappaB表达没有影响。苦参碱减少了由pMCAO诱导的梗死体积，这种效果可能是通过降低NF-kappaB表达实现的。

Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, /the authors/ therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms. Male, Sprague-Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO+oxymatrine 120 mg/kg), low dose (pMCAO+oxymatrine 60 mg/kg) and sham operated group. /The authors/ used a permanent middle cerebral artery occlusion model and administered oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 hr after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-kappaB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hr. Compared with pMCAO group, neurological deficit in high dose group was improved (P < 0.05), infarct volume was decreased (P < 0.001) and cerebral edema was alleviated (P < 0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-kappaB expression was significantly decreased in high dose group. Low dose of oxymatrine did not affect NF-kappaB expression in pMCAO rats. Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者身体前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)