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J Biochem Mol Toxicol. 2019 Feb;33(2):e22251. doi: 10.1002/jbt.22251. Epub 2018 Oct 28.

Mechanism-based inactivation of cytochrome P450 2D6 by chelidonine.

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College of Plant Protection, Shenyang Agricultural University, Liaoning, Shenyang, China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Liaoning, Shenyang, China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou, China.


Chelidonine (CHE) is a major bioactive constituent of greater celandine, a plant used in traditional herbal medicines. CHE has widely been used as an analgesic in clinical settings. We evaluated the inhibitory effects of CHE on human cytochrome P450 enzymes. CHE produced time-, concentration-, and NADPH-dependent inhibition of CYP2D6, with K I and k inact values of 20.49 μM and 11.05 min -1 , respectively. Approximately 76% of CYP2D6 activity was suppressed after 9 minute incubation with CHE (50 μM). The loss of enzyme activity was not restored following dialysis. The estimated partition ratio of the inactivation was about 156. Quinidine, a competitive inhibitor of CYP2D6, attenuated the CHE-mediated enzyme inactivation, while glutathione and catalase/superoxide dismutase did not markedly ameliorate the inhibitory effect. Upon oxidation using potassium ferricyanide, the 15.1% activity of CYP2D6 was restored. These findings indicate that CHE acted as a mechanism-based inactivator of CYP2D6 and the observed effects may induce potential drug-drug interactions.


cytochrome P450 enzymes (CYP); mechanism-based inactivation; metabolic activation

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