Refereed conference paper presented and published in conference proceedings
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) |
全文
| 出版商提供的全文 http://abstracts.aaps.org/Verify/AAPS2016/PosterSubmissions/10T1200.pdf |
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摘要Purpose
As the major alkaloid from Piper nigrum Linn. (black pepper) and Piper longum Linn. (long pepper), piperine has been associated with miscellaneous pharmacologic effects, including antiepileptic effects, anti-tumor properties, anti-oxidative and anti-inflammatory activities. However, few metabolites of piperine have been reported and no study indicated the rate and extent of its metabolism. The current study is proposed to illustrate the phase I metabolism characteristic of piperine.
Methods
Around 35 mg/kg piperine in saline with 20% ethanol was given to rat for 2h. Then liver and bile were collected and treated by protein precipitation method. Potential metabolites of piperine after orally administration in SD rats were subsequently identified by LC/QTOF/MS method. In-vitro enzyme kinetics study was further carried out to explore the hepatic and intestinal metabolic rate and extent of piperine in liver and intestinal microsomes. Piperine ranging from 1 to 160 μM were incubated with 0.5 mg/ml rat liver or intestinal microsomes and NADPH regenerating system for 1.5 h under 37 degree Celsius. The metabolic profile was generated by plotting reaction rate versus concentration of piperine. The enzyme kinetic parameters including maximum velocity (Vmax), substrate concentration at half maximal velocity (Km) and intrinsic clearance (Clint) were further obtained by fitting data to the MichaelisMenten
equation.
Results
After oral administration of piperine, metabolite E,E-1-[5-(3-methoxy-4-hydroxy-phenyl)-1-oxo-2,4 pentadienyl]piperidine was found in both rat liver and bile, and another metabolite, 5-(3,4-methylenedioxy phenyl)-2E,4E- pentadienoic acid-N-(3-yl propionic acid)- amide was identified in bile. The in-vitro enzyme kinetic study showed that piperine had limited hepatic phase I metabolism with Vmax, Km and Clint to be 56.03±5.85 pmol/min/mg, 27.02±9.2 μM and 2.07 μl/min/mg, respectively. In addition, there is no reduction of piperine content after incubation with rat intestinal micosomes, indicating minimal intestinal phase I metabolism.
Conclusion
Our current in-vitro and in-vivo studies consistently indicate that there is no extensive phase I metabolism after consumption of piperine.
着者Ren T., Li C., Wang Q., Zhang Y., 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
语言美式英语
