Journal of Chinese Pharmaceutical Sciences ›› 2021, Vol. 30 ›› Issue (8): 645-656.DOI: 10.5246/jcps.2021.08.052

• Original articles • Previous Articles     Next Articles

In vitro metabolism and inhibitory effects of atractylenolide II on various hepatic CYPs in HLMs

Xulong Chen1,2,3,#, Zhengge Liao1,#, Cheng Li2,3, Guoyong Huang1, Yunyan Song1, Wei Dong1, Abid Naeem1, Xinli Liang1,*()   

  1. 1 Key Laboratory of Modern traditional Chinese Medicine preparations, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
    2 Affiliated Hospital, Jiujiang University, Jiujiang 332000, China
    3 Jiujiang Clinical Precision Medicine Research Center, Jiujiang 332000, China
  • Received:2021-01-12 Revised:2021-03-16 Accepted:2021-05-20 Online:2021-08-29 Published:2021-08-29
  • Contact: Xinli Liang
  • About author:
    # These authors contributed equally to this work.


In the present study, we aimed to investigate the interaction between atractylenolide II (AT-II) and CYP450 enzyme in human liver microsomes, and to lay a theoretical foundation for predicting the possible interaction of AT-II in combination with drugs. The chemical inhibition experiment was carried out with specific inhibitors to clarify the CYP450 subtypes affecting the metabolism of AT-II, and the mechanism, kinetics, and type of inhibition of CYP450 enzyme by AT-II were studied by using the probe-based determination method of human liver microsome system with the related data of IC50 and Ki as evaluation indexes. The metabolism of AT-II was affected by CYP1A2, CYP2C9 and CYP3A4 inhibitors, and the highest inhibition rates were 41.35%, 41.97% and 82.45%, respectively. The IC50 values of AT-II to five subtypes of P450 CYP2C9, CYP1A2, CYP2C19, CYP3A4 and CYP2D6 were 69.7, 84.3, 92.4, 173.8 and 190.1 μmol/L, respectively. The Ki values of AT-II to five subtypes of P450 CYP2C9, CYP1A2, CYP2C19, CYP3A4 and CYP2D6 were 190.6, 179.1, > 200, 72.2 and 66.8, respectively. Among these enzymes, AT-II exhibited non-competitive inhibition on CYP1A2, showed competitive inhibition on CYP2C9 and CYP3A4, and displayed mixed AT-II inhibition on CYP2C19 and CYP2D6. CYP1A2, CYP2C9 and CYP3A4 were involved in the AT-II metabolism, and AT-II exhibited different inhibitory mechanisms and strengths for the five subtypes of CYP450.

Key words: Atractylenolide II, Human liver microsomes, Metabolic phenotype, Enzymatic activity, Drug-drug interaction