Mechanisms for the Efficient Brain Uptake of Piperine after its Oral Administration
Refereed conference paper presented and published in conference proceedings


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AbstractBackground: Piperine, the biological active component in black pepper, served several pharmacologic actions on central nervous system, such as anti-depression, anti-convulsion and neurodegeneration protection. However, the brain uptake of piperine after oral administration has not been well studied. In order to have an integrated evaluation of its brain uptake, multiple aspects need to be considered, including absorption, metabolism, blood & brain tissue binding and brain distribution. So tThe present study is proposed aiming to build up a comprehensive pharmacokinetic profile of piperine to evaluate its brain uptake properties.
Methods: The permeability of piperine first was determined by Caco-2 monolayer model and its. Then phase I and phase II metabolisms in-vitro metabolism studies were conducted evaluated by in-vitro incubation of piperine,with rat liver microsome/ or S9 fraction and in presence of related co-factors for phase I or phase II metabolism. Equilibrium dialysis was applied For to estimate the binding of piperine in plasma and brain homogenate. The binding of piperine to blood was further determined by LC/MS-MS based depletion method. Besides, the unbound volume of distribution in the brain (Vu,brain) was determined by brain slice method. Lastly, the distribution of piperine in brain, plasma and cerebrospinal fluid (CSF) were studied after oral administration of 35xxx mg/kg piperine in Sprague Dawley rats.
Results: In Caco-2 monolayer models, it was found that piperine transported across membrane predominantly by via passive diffusion with Papp values of 5.41±0.40×〖10〗^(-5) cm/sec and 4.78±0.16×〖10〗^(-5) cm/sec for Basalateral to Apical and Apical to Basalateral transport, respectively. With a Clint of 8.15 μl/min/mg, Phase I metabolism of piperine was considered not extensive, which further restricted its further phase II metabolism. Piperine has low binding towards red blood cell with a partition ratio between red blood cells and plasma (KRBC/PL) of 0.27±0.09. In the meantime, it demonstrated high affinity towards brain tissue (98.36-98.46%) and plasma protein (96.22-97.77%) with a brain distribution volume (Vu,brain) of 36.32±1.40 ml/g. The pharmacokinetics study showedprofiles of piperine demonstrated similar concentrations of piperine in brain and plasma after oral administration, with brain to plasma AUC0àinf ratios for total piperine of 0.95and The unbound brain to plasma AUC 0àinf ratiospiperine to be 0.95 was further found to beof 1.10 respectively.. The concentrations in CSF, however, were much lower than that in brain and plasma. The unbound brain to plasma AUC 0àinf ratios was further found to be 1.10. Besides, piperine could evenly distribute to each brain regions.
Conclusions: Piperine could efficiently and homogeneously distribute to brain after oral administration. Its Such high brain exposure could be attributed to its high membrane permeability and with minimal metabolism. The high brain and plasma binding towards of piperine brain and plasma could also contribute to its high efficient brain penetration potency.
All Author(s) ListTianjing Ren, Qianwen Wang, Chenrui Li, Mengbi Yang, Zhong Zuo
Name of ConferenceInternational Symposium for Graduate Students on Pharmaceutical Sciences 2017
Start Date of Conference07/09/2017
End Date of Conference09/09/2017
Place of ConferenceGuangzhou
Country/Region of ConferenceChina
Year2017
LanguagesEnglish-United States
KeywordsPiperine, pharmacokinetics, brain exposure

Last updated on 2018-02-10 at 12:28