Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes

Mollugin originally isolated from Rubia cordifolia is a pharmacological compound for its anti-inflammation, anti-cancer, and anti-viral activity. In the present study, a cocktail probe assay was performed for determination of the selective inhibitory effect of mollugin on cytochrome P450 (CYP) enzymes in human liver microsomes (HLM). Incubation of isoform-specific substrate probes CYPs with mollugin (0–25 μM) in HLM resulted in strong inhibition of CYP1A2-catalyzed phenacetin O-deethylation, showing IC50 values of 1.03 and 3.55 μM without and with pre-incubation, respectively. Mollugin-caused inhibition of phenacetin O-deethylation was concentration-dependent in HLMs, but not time-dependent. In addition, the Lineweaver–Burk plot indicated a typical competitive inhibition. Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2 were comparable. Taken together, the results suggested that mollugin might cause herb–drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia.