Effects of Crocus sativus and its active constituents on cytochrome P450: a review

Cytochrome P450 (CYP) enzymes play an important role in the biotransformation of drugs and endogenous substances. Clinical medications and herbal remedies can either enhance or inhibit the activity of CYP enzymes, leading to potential drug interactions between herbal supplements and prescribed medications. Such interactions can lead to serious consequences, especially for drugs with a narrow therapeutic index, such as digoxin, warfarin, and cyclosporine A. In this review article, we provide an updated review of the impact of saffron, and its active constituents, safranal and crocin, on the 12 major human CYP enzymes and possible drug interactions between saffron and prescription drugs. The available evidence indicates that saffron and its active constituents affect the expression or activity of some CYP isoforms, including the CYP1A1/2, CYP3A4, and CYP2E1 subfamily. Considering the important role of these CYPs in the biotransformation of frequently prescribed medications and the activation of procarcinogen into carcinogenic metabolites, it can be expected that the consumption of saffron and its active constituents may influence the pharmacokinetics and toxicity of several substances. In particular, given the critical role of CYP3A4 in drug metabolism, and saffron's inhibitory impact on this CYP enzyme, it appears that saffron's most significant interaction is linked to its inhibition of CYP3A4. In addition, the inhibitory effect of saffron on CYP1A1/2, and CYP2E1 expression can play a role in the chemopreventive effect of this herbal medicine. Additional research is crucial for evaluating the clinical significance of these interactions in patients who consume saffron along with prescription drugs and determining the dose that can lead to drug interactions. Graphical abstractA schematic diagram of the effect of Crocus sativus and its active constituents on major human cytochrome P450s. CYP: Cytochrome P450.