Abstract
Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, Kp, for the liver and kidney were higher in the piperine-pretreated group, while the Kp for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution. The data demonstrated that the phytochemicals modulated doxorubicin tissue distribution, which suggested their potential to induce food-drug interactions and act as a strategy for the delivery of P-gp substrate drugs to target tissues and tumors.
Highlights
Pungent phytochemicals are consumed worldwide every day
The tissue to plasma partition coefficients, Kp, for the liver and kidney were higher in the piperine-pretreated group, while the Kp for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution
The piperine concentration declined with an elimination half-life capsaicin and [6]-gingerol were eliminated rapidly from plasmafrom withplasma t1/2 values of 0.33 and 1.36 of 6.30 h, capsaicin and [6]-gingerol were eliminated rapidly with t1/2hvalues ofh,0.33 h respectively and were not detected
Summary
The average amount of piperine from black pepper consumed in the U.S was reported to be 21.0 mg/person/day [1]. The maximum daily intake of capsaicin in the U.S and Europe from mild chilies and paprika was estimated to be 1.5 mg/person/day [2,3]. These spicy phytochemicals have been reported to possess various pharmacological activities. They are known to inhibit P-glycoprotein (P-gp) in vitro [4,5,6,7,8].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have