高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (9): 1549-1555.doi: 10.7503/cjcu20170147

• 分析化学 • 上一篇    下一篇

基于光谱分析的姜黄素碱性自氧化及其产物的抗氧化活性

杨昕1, 张迪2, 宋立敏1, 许茜2, 许卉2,3,4(), 刘珂5   

  1. 1. 烟台大学化学与化工学院, 烟台 264005
    2. 药学院,烟台 264005
    3. 分子药理和药物评价教育部重点实验室, 烟台 264005
    4. 新型制剂与生物技术药物研究山东省高校协同创新中心, 烟台 264005
    5. 苏州雷纳药物研发有限公司, 苏州 215123
  • 收稿日期:2017-03-13 出版日期:2017-09-10 发布日期:2017-08-17
  • 作者简介:联系人简介: 许 卉, 女, 博士, 教授, 主要从事创新药物研究与开发方面的研究. E-mail: xuhui33@sina.com
  • 基金资助:
    国家十二五“重大新药创制”科技重大专项课题(批准号: 2014ZX09301306-006)和烟台大学2017年研究生科技创新基金(批准号: YDYB1725)资助

Spectroscopic Studies on Alkaline Autoxidation of Curcumin and Antioxidative Activities of the Product

YANG Xin1, ZHANG Di2, SONG Limin1, XU Qian2, XU Hui2,3,4,*(), LIU Ke5   

  1. 1. School of Chemistry and Chemical Engineering, Yantai 264005, China
    2. School of Pharmacy, Yantai 264005, China
    3. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai 264005, China
    4. Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
    5. Suzhou Nanomedicine R&D Co. Ltd., Suzhou 215123, China
  • Received:2017-03-13 Online:2017-09-10 Published:2017-08-17
  • Contact: XU Hui E-mail:xuhui33@sina.com
  • Supported by:
    † Supported by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Twelfth Five-year Plan Period, China(No.2014ZX09301306-006) and 2017 Graduate Science and Technology Innovation Fund of Yantai University, China(No;YDYB1725)

摘要:

在室温及弱碱性条件下进行姜黄素自氧化反应, 应用柱色谱分离、 紫外吸收光谱(UV)、 红外光谱(IR)、 核磁共振波谱(NMR)和质谱(MS)等分析技术, 分离并鉴定了主要自氧化产物的化学结构. 针对反应进程, 采用高效液相色谱-二极管阵列检测器(HPLC-DAD)分析技术, 从底物消除和产物生成2个方面进行了定性及定量研究. 以抗坏血酸作阳性对照, 采用1,1-二苯基-2-三硝基苯肼自由基(DPPH·)、 羟自由基(·OH)和超氧阴离子自由基(O2-·)体系, 定量比较了产物和姜黄素的体外抗氧化活性. 结果表明, 姜黄素在室温及弱碱性条件下的降解消除以自氧化反应为主, 姜黄素消除过程和自氧化产物生成过程均符合一级动力学特征. 自氧化产物具有双环乙酰丙酮的骨架结构, 并显示有DPPH·, ·OH和O2-·等自由基清除活性, 但作用强度均显著低于姜黄素, 因此在姜黄素应用过程中应严格控制pH条件, 避免发生自氧化反应.

关键词: 姜黄素, 自氧化反应, 双环乙酰丙酮, 抗氧化活性, 光谱分析

Abstract:

Curcumin is a natural antioxidant with strong biological and chemical activity. The curcumin degradation was carried out under weak alkaline conditions at room temperature, integrated used by means of column chromatography, UV, IR, NMR, MS and other spectral analysis techniques, the chemical structure of the major degradation products was isolated and identified. For the reaction process, the qualitative and quantitative studies were carried out from two aspects: substrate elimination and product formation by HPLC-DAD spectroscopy analysis technology. Ascorbic acid was used as a positive control, and its antioxidant activities were evaluated in vitro, by 1,1-diphenl-2-picrylhyrazyl free radical(DPPH·), hydroxyl radical(·OH) and superoxide radical(O2-·) scavenging assays, and compared with curcumin quantitatively. The results showed that the main degradation of curcumin at room temperature under weak alkaline conditions was autoxidation reaction, both of which conformed to the first order kinetics. the structure of heptadiene -3,5-diketone in curcumin[(1E,6E)-1,7-bis-(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] forms a quinone methide intermediate in the presence of alkaline environment, after a series of oxygenation, hydration, dehydration and rearrangement, the target compounds bicyclopentadiones was a cyclization product with a tetrahydrofuran ring and cyclopentanedione structure in the molecule, we named CURC[6-hydroxy-1-(4-hydroxy-3-methoxyphenoxy)-3-(4- hydroxy-3-methoxyphenyl)-1,3,3a,6a-tetrahydro-4H-cyclopenta[c]furan-4-one]. Based on the established stable and reliable spectrophotometric system, the results of in vitro free radical scavenging activity of CURC and curcumin are as follows. CURC has a certain scavenging activity on DPPH·, ·OH and O2-·, but the action intensity is significantly lower than that of curcumin. The EC50 values were 0.17 mmol/L and 0.022 mmol/L in the DPPH assay, 0.33 mmol/L and 0.098 mmol/L in the ·OH assay as well as 0.38 mmol/L and 0.056 mmol/L in the O2-· assay, respectively. The obtained results suggest that the pH condition should be strictly controlled during the application of curcumin and avoid the autoxidation reaction.

Key words: Curcumin, Alkaline autoxidation, Bicyclopentadiones, Antioxidant activity, Spectral analysis

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