牛成, 王东阁, 张天宏, 温鸿亮. 姜黄素琥珀酸酯前药的合成及其抗炎活性评价J. 药学学报, 2018,53(12): 2085-2092. doi: 10.16438/j.0513-4870.2018-0882
引用本文: 牛成, 王东阁, 张天宏, 温鸿亮. 姜黄素琥珀酸酯前药的合成及其抗炎活性评价J. 药学学报, 2018,53(12): 2085-2092. doi: 10.16438/j.0513-4870.2018-0882
NIU Cheng, WANG Dong-ge, ZHANG Tian-hong, WEN Hong-liang. Synthesis and anti-inflammatory activity of curcumin succinate prodrugsJ. Acta Pharmaceutica Sinica, 2018,53(12): 2085-2092. doi: 10.16438/j.0513-4870.2018-0882
Citation: NIU Cheng, WANG Dong-ge, ZHANG Tian-hong, WEN Hong-liang. Synthesis and anti-inflammatory activity of curcumin succinate prodrugsJ. Acta Pharmaceutica Sinica, 2018,53(12): 2085-2092. doi: 10.16438/j.0513-4870.2018-0882

姜黄素琥珀酸酯前药的合成及其抗炎活性评价

Synthesis and anti-inflammatory activity of curcumin succinate prodrugs

  • 摘要: 姜黄素是一种从姜科姜黄属植物中提取得到的多酚类化合物,具有抗炎、抗肿瘤等多种生物活性。但姜黄素水溶性差,限制了它在临床的使用。根据姜黄素的结构特征,本文设计合成了姜黄素一取代和二取代琥珀酸酯前体药物并对它们的溶解度、稳定性、大鼠体内的代谢及抗炎活性进行了研究(实验所用大鼠由军事医学科学院北京实验动物中心提供,经伦理委员会批准且实验均按照相关指导原则和规定进行),结果表明:合成的姜黄素琥珀酸酯前体药物在水中的溶解度比姜黄素提高约300倍,姜黄素一取代琥珀酸酯在水和磷酸缓冲溶液中的半衰期分别为6.55和5.56 h,姜黄素二取代琥珀酸酯在水和磷酸缓冲溶液中的半衰期分别为6.81和3.48 h;进入大鼠体内,姜黄素琥珀酸酯前体药物可迅速完全转变为姜黄素;抗炎实验显示,经尾静脉注射给药后,姜黄素琥珀酸酯前体药物对鸡蛋清诱导的大鼠足跖肿胀模型产生明显的抗炎作用,与同等剂量下地塞米松的抗炎活性相当。

     

    Abstract: Curcumin, a polyphenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of anti-inflammatory and antitumor activities. Despite the promising biological effects of curcumin, its poor solubility has restricted its use in the management of human ailments. To improve its water-solubility, curcumin succinate prodrugs were designed and synthesized and their aqueous solubility, stability, metabolism in rats and anti-inflammatory activity were evaluated (experiments had been approved by the ethics committee and carried out in accordance with the relevant guidelines and regulations; rats were provided by Beijing courtyard experimental animal center of Academy of Military Medical Sciences). The results showed that curcumin succinate prodrugs are very soluble in water and more stable than curcumin in water and in phosphate buffer solution. They released curcumin rapidly and quantitatively after intravenous administration. In phlogogen-induced paw edema in rats, curcumin succinate prodrugs showed anti-inflammatory activity as potent as dexamethasone.

     

/

返回文章
返回