Yan Miao, Li Lanfang, Li Huande, Fang Pingfei, Xu Ping, Zheng Mei, Xu Danhua
Clinical Pharmacy & Pharmacology Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhongguo Zhong Yao Za Zhi. 2012 Jan;37(1):99-103.
The aim of the present study was to evaluate the modulating effect of glycyrrhizic acid C-18 epimers, 18alpha-glycyrrhizic acid (alpha-GL) and 18beta-glycyrrhizic acid (beta-GL) on both P-glycoprotein (P-gp) activity and expression in Caco-2 cell.
The effects of P-gp activity were analyzed by rhodamine (Rhd 123) accumulation test, and those of P-gp expression were analyzed by flow cytometry and real-time PCR.
At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL inhibited the function of P-gp and with on dose dependent while beta-GL induced the function of P-gp at three test concentrations with no dose dependent too. At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL down-regulated the expression of MDR1 mRNA. At high concentrations (60 micromol x L(-1)), beta-GL up-regulated the expression of MDR1 mRNA; At high concentrations (60 micromol x L(-1)), beta-GL induced the expression of P-gp protein while alpha-GL has no effect on the expression of P-gp protein at three test concentrations.
The effects of alpha-GL and beta-GL on the expression of MDR1 mRNA and CYP3A mRNA showed the same trend. The character that epimers of GL act on CYP3A and P-gp show similar stereo selectivity whether relate to PXR need further study.
本研究旨在评估甘草酸C-18差向异构体18α-甘草酸（α-GL）和18β-甘草酸（β-GL）对Caco-2细胞中P-糖蛋白（P-gp）活性及表达的调节作用。
通过罗丹明（Rhd 123）蓄积试验分析P-gp活性的影响，通过流式细胞术和实时定量PCR分析P-gp表达的影响。
在中、高浓度（10、60 μmol·L⁻¹）时，α-GL抑制P-gp功能且呈剂量依赖性，而β-GL在三个测试浓度下均诱导P-gp功能且无剂量依赖性。在中、高浓度（10、60 μmol·L⁻¹）时，α-GL下调MDR1 mRNA的表达。在高浓度（60 μmol·L⁻¹）时，β-GL上调MDR1 mRNA的表达；在高浓度（60 μmol·L⁻¹）时，β-GL诱导P-gp蛋白表达，而α-GL在三个测试浓度下对P-gp蛋白表达均无影响。
α-GL和β-GL对MDR1 mRNA和CYP3A mRNA表达的影响呈现相同趋势。甘草酸差向异构体作用于CYP3A和P-gp所表现出的类似立体选择性是否与孕烷X受体相关，有待进一步研究。
