Enhancement by adrenaline of ginsenoside Rg1 transport in Caco-2 cells and oral absorption in rats.
OBJECTIVE
The purpose of this research was to evaluate the ability of adrenaline (epinephrine) to stimulate the uptake of ginsenoside Rg1 (Rg1) by Caco-2 cells.


METHODS
Rg1 uptake was measured using Caco-2 cell monolayers. The Rg1 uptake medium with adrenaline at different concentrations was added to each well and incubated for different time intervals. Adrenergic antagonists such as phentolamine and propranolol were added to the incubation medium to investigate their effects on Rg1 uptake. The Rg1 concentration in the monolayers was determined by high-performance liquid chromatography. Transport of Rg1 across Caco-2 cells was also studied and an oral bioavailability study of Rg1 was carried out in rats.


RESULTS
The incubation medium with adrenaline remarkably increased the amount of Rg1 uptake by Caco-2 cells. Adrenaline-induced Rg1 transport increased in a dose- and time-dependent manner. The effect of adrenergic antagonists on adrenaline-induced uptake of Rg1 was investigated and it was found that the enhancement effect was attenuated by the co-treatment with propranolol but not phentolamine. The transport amount of Rg1 by Caco-2 cells increased in response to 1 mM adrenaline, isoproterenol or salbutamol. In contrast, 1 mM phenylephrine had no effect on Rg1 transport in Caco-2 cells. The effect of adrenaline on the absorption of Rg1 was further investigated in vivo in rats. The co-administration with adrenaline in rats showed that the oral bioavailability was increased remarkably relative to the aqueous solution. The area under the plasma concentration-time curve of Rg1 after co-administration with 1 mM adrenaline was 79.1 +/- 31.04 microg/ml/h compared with 2.81 +/- 1.13 microg/ml/h for its aqueous solution.


CONCLUSIONS
Adrenaline is effective for the stimulation of intestinal absorption of Rg1 and the enhanced absorption is mediated mainly by the interaction of adrenaline with beta2-adrenoceptors.
Xiong
Jing
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, PR China.
Sun
Minjie
M
Guo
Jianxin
J
Huang
Luosheng
L
Wang
Shujing
S
Meng
Boyu
B
Ping
Qineng
Q
D000284:Administration, Oral; D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D036145:Ginsenosides / Q000493:pharmacokinetics*; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D002491:Central Nervous System Agents; D036145:Ginsenosides; C035054:ginsenoside Rg1; D004837:Epinephrine