Other conference paper
香港中文大学研究人员 ( 现职)
| 左中教授 (药剂学院) |
| 张玉峰博士 (药剂学院) |
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| 出版商提供的全文 http://abstracts.aaps.org/Verify/AAPS2016/PosterSubmissions/08M1200.pdf |
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摘要Purpose
Piperine is the major bioactive compound from Piper nigrum Linn. (black pepper) and Piper longum Linn. (long pepper). Due to the conjugated double bonds structure, piperine has three geometrical isomers namely isopiperine, chavicine, and isochavicine. Although the isomerization was reported to be initiated by exposure to sunlight or UV light, whether it could occur in-vivo or in biological matrix has not been studied before. The present study aims to investigate the existence of piperine isomerization in absence of light under various experimental conditions including a) in-vitro incubation temperature and duration in stock solution and biological matrix of rat plasma and liver microsomes and b) in-vivo rat plasma samples after piperine administrations.
Methods
Piperine and its three isomers were separated by an HPLC/UV system consisting Waters 2690 LC System with Waters 996 Photodiode Array UV detector. The separation was achieved by Agilent ZORBAX Eclipse XDB C18 column (250 × 4.6mm, 5μm) using isocratic solvent system consisting of 50% acetonitrile and 50% H2O with 0.1% formic acid at 0.4 ml/min. Theoretical UV spectrum of piperine and its isomers in methanol were obtained by performing Time Dependent Density Functional Theory (TD-DFT) calculations (provided in Gaussian 09).
Piperine was incubated in amber tube in DMSO for different duration and temperature. The incubation was also conducted with rat plasma and rat liver microsome at 37 for different time interval mimicking the biological condition. Then single intravenous bolus of piperine was further administrated to SD rats (N=4) at 3.5 mg/kg and blood samples were collected at 5, 10, 30, 60, 90, 120, 240, 360, 480 min. The sample was treated with protein precipitation method by adding three times volume of methanol/acetonitrile (1:1, v/v). During all experiment procedure, samples were protected from light to minimize or avoid photoisomerization.
Results
By comparing with the theoretical and experimental UV spectra of piperine and its isomers, we identified three piperine isomers in HPLC/UV chromatograms as chavicine, isopiperine and isochavicine at retention times of 27.1 min, 28.2 min and 30.1 min, respectively. The UV spectra of piperine, chavicine, isopiperine and isochavicine were comparable with the calculated spectra obtained from TD-DFT with respective λmax of 341 nm, 314 nm, 331 nm and 329 nm. Under in-vitro incubation conditions, the percentages of formation of three isomers were less than 1% at different incubation time and temperature. In addition, no isomerization was found after piperine incubation with plasma or microsome. The longer incubation time did not lead to further isomerization. Consistent with in-vitro incubation findings, only less than 1 % of 3 isomers were found in rat plasma sample after i.v. administration of piperine in rats.
Conclusion
Under both in-vitro and in-vivo situations, light seems to be the major contributing factor for the isomerization of piperine. If it is protected from light, no isomerization of piperine will occur in biological matrix or in-vivo.
着者Ren T., Zhang Y., Li C., Wang Q., Zuo Z.
会议名称2016 AAPS Annual Meeting and Exposition
会议开始日13.11.2016
会议完结日17.11.2016
会议地点Denver, CO
会议国家美国
出版年份2016
月份11
语言美式英语
