Effects Of Glycyrrhizic Acid And Glycyrrhetinic Acid On P - Glycoprotein Function And Its Expression

Glycyrrhizin (GL) and its aglycone glycyrrhetic acid (GA) are major bioactives derived from Glycyrrhiza plants (liquorice), the important oriental phytomedicine and worldwide food additive. This study investigated the effects of the two widely used clinical drugs, Glycyrrhizin and glycyrrhetic acid, on the function and expression of P-glycoprotein (P-gp), and provide the scientific basis for the drugs’ clinical application and development. The propose of this work is to clarify the potential active-transporter interactions in gastrointestinal absorption of the herbal actives after co-oral administration of the liquorice components. The cytotoxicities of GL/GA to Caco-2cells were evaluated by the MTT assay, to ensure the percentage of cell viability in the subsequent studies. The effects of GL/GA on P-gp activity were evaluated by P-gp substrate Rh123accumulation, which was measured using microplate reader. The effects of GL/GA on expressions of P-gp at the protein level and MDR1mRNA were detected by Western blot and RT-qPCR, respectively. The results showed that Caco-2cells exposed to GL and GA for48h exhibited decreased P-gp expression activity at protein and evidently inhibited MDR1mRNA level. P-gp function, as established by Rhodamine123(Rh123) intracellular accumulation, was correlated with decreasing P-gp expression. These findings revealed that GL and GA had a synergetic effect on potentially improving oral absorption of the P-gp substrates in vitro, but they worked in distinct ways. The inhibitions on expression of P-gp or MDR1mRNA were indispensable mechanisms for the both components to modulate P-gp-mediated efflux.