Walnut Compound Juglone Blocks Key Drug-Metabolizing Enzyme CYP2C9 in Lab

A compound extracted from walnut green husks, juglone, has shown strong inhibitory activity against CYP2C9, a major liver enzyme involved in processing widely used drugs such as warfarin, sulfonylureas and phenytoin. Researchers at East China Normal University tested juglone in enzyme assays reported in Frontiers in Pharmacology, examining its effects on six key CYP enzymes using human liver microsomes and rat liver microsomes. In human preparations, CYP2C9 was the most vulnerable activity, with an IC50 of 8.12 micromolar and competitive inhibition parameters including an apparent Ki of 4.97 micromolar. CYP2E1 ranked next, with IC50 of 12.67 micromolar and mixed inhibition. The study notes this is not a demonstrated clinical interaction but provides kinetic baseline data for regulators.