作者: Chong-Zhen Qin , Qiao-Li Lv , Na-Yiyuan Wu , Lin Cheng , Yun-Chen Chu
DOI: 10.1016/J.JEP.2015.03.061
关键词:
摘要: Abstract Ethnopharmacological relevance Alantolactone (AL), one of the main active ingredients in Inula helenium L. , has been included various prescriptions traditional Chinese medicine. The effects AL on cytochrome P450 (CYP450) were still unclear. This study evaluated inhibitory effect P450s vitro and vivo . Materials methods CYPs activity human liver microsomes (HLMs) recombinant cDNA-expressed enzymes incubation system, then determined by LC-MS/MS based probe substrate assay. C57BL/6 mice treated orally (0, 25, 50, 100 mg/kg) for 15 days. major Cyps examined at both mRNA enzyme levels. Results showed a potent CYP3A4 with IC 50 values 3.599 3.90 (recombinant CYP3A4) μM, respectively. strongly decreased dose-dependent but not time-dependent way HLMs. from typical Lineweaver–Burk plots that could inhibit noncompetitively, Ki value 1.09 μM Moreover, CYP2C19 also be inhibited 36.82 μM. Other CYP450 isoforms markedly affected AL. inhibition was validated mice. significantly expression Cyp2c 3a family. Conclusion indicates herb–drug interaction should paid more attention between drugs metabolized CYP3A4.