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

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 ±â€¯0.22, after: 0.44 ±â€¯0.14; p = 0.002) and ∼6.0% in urine (before: 3.81 ±â€¯1.20, after: 3.58 ±â€¯0.92; p = 0.054). CYP1A2 index was significantly reduced only in males (saliva, before: 0.65 ±â€¯0.22, after: 0.51 ±â€¯0.16; p = 0.0001; urine, before: 4.53 ±â€¯1.19, after: 4.03 ±â€¯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.

Dietary effects of Sideritis scardica "mountain tea" on human in vivo activities of xenobiotic metabolizing enzymes in healthy subjects.

Sideritis scardica(S. scardica) is an endemic plant of the Balkan Peninsula traditionally used as herbal tea for inflammation and gastric disorders. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The purpose of the present study was to determine whether S. scardica decoction alters the activity of CYP1A2, CYP2A6, XO, NAT2 and UGT1A1/1A6 enzymes in humans. Fourteen healthy subjects consumed S. scardica decoction for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine and paracetamol metabolite ratios as follows: CYP1A2: 17X/137X (saliva) and (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X), NAT2: AFMU/(AFMU+1U+1X) and UGT1A1/1A6: glucuronidated/total paracetamol (urine). After S. scardica intake, CYP1A2 index was reduced by ∼16% and ∼8% in saliva (before: 0.54 ±â€¯0.18, after: 0.46 ±â€¯0.09; p = 0.08) and urine (before: 3.59 ±â€¯0.52, after: 3.67 ±â€¯0.78; p = 0.12), respectively. CYP2A6 index was significantly reduced only in males (before: 0.76 ±â€¯0.08, after: 0.67 ±â€¯0.07; p = 0.004), suggesting sexual dimorphism in CYP2A6 inhibition. There was no effect of Sideritis scardica treatment on XO, NAT2 or UGT1A1/1A6 indices. Usual consumption of the aerial parts of S. scardica decoction is unlikely to result in herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP2A6 substrate interaction in males.

Effects of peppermint tea consumption on the activities of CYP1A2, CYP2A6, Xanthine Oxidase, N-acetyltranferase-2 and UDP-glucuronosyltransferases-1A1/1A6 in healthy volunteers.

Peppermint leaves are widely used for the symptomatic treatment of digestive disorders. Previous studies have shown significant effects of its natural products on human enzyme activity; however, there is no study available concerning the effects of peppermint tea on metabolizing enzymes in humans. Aim of the present study was to investigate the effect of peppermint tea on CYP1A2, CYP2A6, Xanthine Oxidase (XO), N-acetyltranferase-2 (NAT2) and UDP-glucuronosyltransferases-1A1/1A6 (UGT1A1/1A6) activities in healthy subjects. Four males and five females consumed peppermint tea (2 g of dry leaves/200 mL water, twice daily) for six days. CYP1A2, CYP2A6, XO, NAT2 and UGT1A1/1A6 activities were determined before and at the end of the study period, using the following caffeine and paracetamol metabolic ratios: CYP1A2: 17MX/137MX (saliva) and (AFMU+1MU+1MX)/17MU (urine); CYP2A6: 17MU/(17MU + 17MX), XO: 1MU/(1MU+1MX), NAT2, AFMU/(AFMU+1MU+1MX) and UGT1A1/1A6 glucuronidated/total paracetamol, all determined in urine. NAT2 metabolic ratio was significantly reduced following peppermint consumption (0.15 ± 0.13 vs 0.14 ± 0.13; p < 0.05). CYP1A2 urine and saliva indices were reduced, yet not significantly, following peppermint consumption (urine: 3.17 ± 1.08 vs 2.91 ± 0.76, saliva: 0.56 ± 0.12 vs 0.50 ± 0.12; p > 0.05). Peppermint had no influence on CYP2A6, XO and UGT1A1/1A6 indices. Daily ingestion of peppermint tea may alter pharmacokinetics of clinically administered drugs and promote cancer chemoprevention through NAT2 inhibition.