Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine  

作　　者：JIN Zhao-Hui QIU Wen LIU Hui JIANG Xue-Hua WANG Ling 

机构地区：[1]West China School of Pharmacy, Sichuan University, Chengdu 610041, China [2]Department of Pharmacy, West China Hospital, Chengdu 610041, China [3]Lanzhou University Second Hospital, Lanzhou 730030, China

出　　处：《Chinese Journal of Natural Medicines》2018年第2期143-149,共7页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81573789)

摘　　要：Ginsenoside Rh2(Rh2)is one of the major bioactive ginsenosides in Panax ginseng.However,the oral bioavailability of Rh2 is low,with P-glycoprotein(P-gp)and CYP3A4 being reported to be the main factors.The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2.The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system,respectively.The pharmacokinetics of oral Rh2(10 mg·kg^(-1))administered alone or in combination with piperine(10 and 20 mg·kg^(-1))was performed in rats.The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine.The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2.The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose(20 mg·kg^(-1))when compared to the control group,with relative bioavailability of 196.8%.The increase of Rh2 exposure led to increased serum levels of IL-12.In conclusion,piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.Ginsenoside Rh2（Rh2）is one of the major bioactive ginsenosides in Panax ginseng.However,the oral bioavailability of Rh2 is low,with P-glycoprotein（P-gp）and CYP3A4 being reported to be the main factors.The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2.The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system,respectively.The pharmacokinetics of oral Rh2（10 mg·kg^（-1））administered alone or in combination with piperine（10 and 20 mg·kg^（-1））was performed in rats.The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine.The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2.The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose（20 mg·kg^（-1））when compared to the control group,with relative bioavailability of 196.8%.The increase of Rh2 exposure led to increased serum levels of IL-12.In conclusion,piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.

关 键 词：PANAX GINSENG GINSENOSIDE Rh2 PIPERINE Immune modulation Bioenhaneer 

分 类 号：R969.1[医药卫生—药理学]