Effects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers

Abstract

Crocus sativus L., a perennial plant grown mainly around the Mediterranean and Iran, has many medicinal properties including anti-inflammatory, anti-depressive and cancer preventing properties. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The present study was designed to determine whether C. sativus infusion alters the activity of CYP1A2, CYP2A6, XO and NAT2 enzymes in humans.Thirty-four healthy volunteers consumed infusion prepared from C. sativus stigmata for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine metabolite ratios as follows: CYP1A2: 17X/137Χ (saliva) and CYP1A2: (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X) and NAT2: AFMU/(AFMU+1U+1X) (urine).Following C. sativus intake, CYP1A2 index was reduced by ∼13.7% in saliva (before: 0.51 ± 0.22, after: 0.44 ± 0.14; p = 0.002) and ∼6.0% in urine (before: 3.81 ± 1.20, after: 3.58 ± 0.92; p = 0.054). CYP1A2 index was significantly reduced only in males (saliva, before: 0.65 ± 0.22, after: 0.51 ± 0.16; p = 0.0001; urine, before: 4.53 ± 1.19, after: 4.03 ± 0.87; p = 0.017) suggesting sexual dimorphism in CYP1A2 inhibition. There was no effect of C. sativus intake on CYP2A6, XO or NAT2 indices.Short-term consumption of C. sativus infusion is unlikely to result in significant herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP1A2 substrate interaction in males.