(1R,2R,9S,13S,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one | 16837-52-8

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 天然来源抗感染药
• 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: (1R,2R,9S,13S,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one
• CAS: 16837-52-8
• 化学式: C15H24N2O2
• 分子量: 264.36
• InChiKey: XVPBINOPNYFXID-KAHWEZKRSA-N

物化性质

• 熔点：
  208℃
• 溶解度：
  可溶于甲醇：10mg/mL，澄清，无色
• 颜色/状态：
  White to off-white powder
• 气味：
  Slight amber aroma
• 蒸汽压力：
  8.75X10-11 mm Hg at 25 °C (est)
• 亨利常数：
  Henry's Law constant = 1.04X10-18 atm-cu m/mol at 25 °C (est)

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

丹参（Oliv.）Diels和白芍药Ait.的配伍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）分别是丹参（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组合的协同抗炎作用，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水肿模型和角叉菜胶诱导的大鼠足跖水肿模型评价了SF和OMT组合的抗炎效果。在体外，通过实时PCR（RT-PCR）微阵列分析测定了脂多糖（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）测量了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组合能显著抑制二甲苯诱导的小鼠耳水肿和角叉菜胶诱导的大鼠足跖水肿，而单独使用上述剂量的每种药物时没有发现效果。与单独使用SF或OMT相比，该组合在下调LPS刺激的RAW 264.7细胞中炎症相关介质的mRNA表达方面表现出更好的效果。ELISA结果显示，该组合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组合显示出协同抗炎作用，其活性可能与其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

邻甲氧基补骨脂素（OMT）是从中国药材中提取出来的化合物，多年来在中国临床上分别用于治疗心脏病和肝病。本研究的目的是探讨OMT的镇痛效果及其作用机制。通过醋酸扭体实验和福尔马林实验等动物疼痛模型，发现OMT在剂量依赖性方式下显示出显著的镇痛效果。在体外实验中，OMT处理抑制了辣椒素诱导的背根神经节细胞内钙浓度的增加。重要的是，全细胞膜片钳技术显示OMT对辣椒素诱导的电流有协同抑制作用。我们的结果表明，OMT产生显著的镇痛效果，可能与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来实现的。作者们因此研究了苦参碱对大脑缺血损伤的潜在神经保护作用及其机制。雄性Sprague-Dawley大鼠被随机分配到四个组：永久性大脑中动脉闭塞（pMCAO），高剂量组（pMCAO+苦参碱120 mg/kg），低剂量组（pMCAO+苦参碱60 mg/kg）和假手术组。作者们使用永久性大脑中动脉闭塞模型，在大脑缺血后立即腹腔注射苦参碱，并在接下来的几天内每天注射一次。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氯化物（TTC）染色分析梗死体积。与pMCAO组相比，高剂量组的神经缺陷得到改善（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表达来实现的。

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毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，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。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，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。寻求医疗帮助。 /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)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S24/25
• 危险类别码：
  R22,R20/22
• WGK Germany：
  3
• 海关编码：
  29399990
• 危险品运输编号：
  NONH for all modes of transport

制备方法与用途

天然生物碱——氧化苦参碱（oxymatrine）是一种广泛存在于豆科槐属植物中的天然生物碱，主要存在于苦参（Sophora flavescens Ait.）、越南槐（S. tonkinensis Gagnep）和白刺花（S. viciifolia Hance）中。氧化苦参碱属于喹诺里西啶类生物碱，具有广泛的生物活性，如抗炎、抗肿瘤、镇痛、调节心率、镇咳和杀菌等作用。

其氮原子以配位键与氧结合，研究表明，在某些条件下，氧化苦参碱可转化为苦参碱。此外，这类生物碱还广泛应用于农业，用于防治松毛虫、茶毛虫、菜青虫等多种害虫，并具有杀虫、杀菌及调节植物生长等功能。

性质

• 外观：白色结晶性粉末；气微，味苦。

应用

• 苦参素被广泛应用于医药、农药和兽药等领域。它具有抗肿瘤、抗菌、抗寄生虫、抗炎、消肿利尿及减轻环磷酰胺引起的白细胞减少等作用。在抗肿瘤方面，氧化苦参碱能够降低谷-丙转氨酶水平，并有助于治疗慢性乙型肝炎（CHB），调节机体免疫状态和改善肝功能。

生物活性

• 氧化苦参碱是一种从Sophora flavescens的根部分离出的喹唑啉生物碱，具有抗炎症、抗纤维化及抗肿瘤活性。它能抑制iNOS表达并阻断TGF-β/Smad通路，用于治疗病毒性肝炎、癌症、病毒性心肌炎和皮肤疾病（如阴道炎、银屑病和湿疹）。

体外研究

• 氧化苦参碱能够保护小鼠免受GalN/LPS诱导的爆发性肝炎，并通过下调肝脏中血清肿瘤坏死因子α的产生及Fas和Fas配体的表达，抑制肝细胞凋亡及其随后的坏死。此外，它还表现出对乙型肝炎病毒的体外抗作用。

体内研究

• 氧化苦参碱的半数致死剂量（LD50）为小鼠腹腔注射521毫克/千克、静脉注射150毫克/公斤。

化学性质

• 外观：无色块状结晶，易溶于氯仿和甲醇，难溶于石油醚和丙酮。来源于山豆根及苦参。

用途

• 主要用于含量测定、鉴定以及药理实验等。具有利尿作用，并对肺癌和胃癌细胞诱导的血管内皮细胞增殖有抑制作用。

类别

• 毒性：属于有毒物质，属中毒类。
• 急性毒性：
  • 腹腔注射小鼠 LD50：521 毫克/公斤；
  • 静脉注射小鼠 LD50: 150 毫克/公斤。

危险特性

• 可燃性：可燃；火场分解产生有毒氮氧化物烟雾。
• 储运特性：库房低温通风、干燥保存。

灭火剂

• 可用水、二氧化碳、干粉或砂土进行灭火。