Assessment of the CYP1A2 Inhibition-Mediated Drug Interaction Potential for Pinocembrin Using In Silico, In Vitro, and In Vivo Approaches

Pinocembrin, a bioflavonoid, is extensively used in complementary/alternative medicine. It turns out as a promising candidate against neurodegenerative diseases because of its multi-faceted pharmacological action toward neuroprotection. However, literature evidence is still lacking for its inhibitory action on CYP1A2, which is responsible for xenobiotic metabolism leading to the generation of toxic metabolites and bioactivation of procarcinogens. In the present study, our aim was to evaluate the CYP1A2 inhibitory potential of pinocembrin via in silico, in vitro, and in vivo investigations. From the results of in vitro studies, pinocembrin is found to be a potent and competitive inhibitor of CYP1A2. In vitro-in vivo extrapolation results indicate the potential of pinocembrin to interact with CYP1A2 substrate drugs clinically. Molecular docking-based in silico studies demonstrate the strong interaction of pinocembrin with human CYP1A2. In in vivo investigations using a rat model, pinocembrin displayed a marked alteration in the plasma exposure of CYP1A2 substrate drugs, namely, caffeine and tacrine. In conclusion, pinocembrin has a potent CYP1A2 inhibitory action to cause drug interactions, and further confirmatory study is warranted at the clinical level.

Automated summary

Pinocembrin, a potential drug candidate for neurodegenerative diseases, has been found to have a potent inhibitory action on CYP1A2, an enzyme responsible for xenobiotic metabolism. In vitro and in silico studies demonstrate the strong interaction between pinocembrin and CYP1A2, and in vivo investigations using a rat model confirm its potential to cause drug interactions. Further clinical studies are warranted to confirm these findings.