| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Qin, Chong-Zhen Lv, Qiao-Li Wu, Na-Yiyuan Cheng, Lin Chu, Yun-Chen Chu, Tang-Yuan Hu, Lei Cheng, Yu Zhang, Xue Zhou, Hong-Hao |
| Description |
Author Affiliation: Qin CZ ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Lv QL ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Wu NY ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Cheng L ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Chu YC ( Department of Molecular Biology and Human Genetics, Tzu Chi University. No 701 Sec 3 Chun Yang Rd. Hualian City, Taiwan.); Chu TY ( Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan); Hu L ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Cheng Y ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China); Zhang X ( Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.); Zhou HH ( Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China) |
| Abstract |
ETHNOPHARMACOLOGICAL RELEVANCE: Alantolactone (AL), one of the main active ingredients in Inula helenium L., has been included in various prescriptions of traditional Chinese medicine. The effects of AL on cytochrome P450 (CYP450) were still unclear. This study evaluated the inhibitory effect of AL on cytochrome P450s in vitro and in vivo. MATERIALS AND METHODS: The inhibitory effects of AL on the CYPs activity were evaluated in human liver microsomes (HLMs) and recombinant cDNA-expressed enzymes incubation system, and then determined by LC-MS/MS based CYPs probe substrate assay. C57BL/6 mice were treated AL orally (0, 25, 50, 100 mg/kg) for 15 days. The inhibitory effects of AL on major Cyps in mice were examined at both the mRNA and enzyme activity levels. RESULTS: AL showed a potent inhibitory effect on CYP3A4 activity with IC50 values of 3.599 (HLMs) and 3.90 (recombinant CYP3A4) µM, respectively. AL strongly decreased CYP3A4 activity in a dose-dependent but not time-dependent way in HLMs. Results from typical Lineweaver-Burk plots showed that AL could inhibit CYP3A4 activity noncompetitively, with a Ki value of 1.09 µM in HLMs. Moreover, activity of CYP2C19 could also be inhibited by AL with IC50 of 36.82 µM. Other CYP450 isoforms were not markedly affected by AL. The inhibition was also validated by in vivo study of mice. AL significantly decreased mRNA expression of Cyp2c and 3a family. CONCLUSION: The study indicates that herb-drug interaction should be paid more attention between AL and drugs metabolized by CYP3A4. |
| File Format |
HTM / HTML |
| ISSN |
03788741 |
| Volume Number |
168 |
| e-ISSN |
18727573 |
| Journal |
Journal of Ethnopharmacology |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2015-06-20 |
| Publisher Place |
Ireland |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Ethnopharmacology Cytochrome P-450 Enzyme Inhibitors Pharmacology Cytochrome P-450 Enzyme System Metabolism Lactones Sesquiterpenes, Eudesmane Animals Genetics Humans Liver Drug Effects Enzymology Male Mice Mice, Inbred C57bl Microsomes, Liver Journal Article |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Drug Discovery Pharmacology |
