In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato

Nair, Vipin D. P.; Foster, Brian; Arnason, John T.; Mills, Edward J.; Kanfer, Isadore

doi:10.1016/j.phymed.2006.12.004

Cited by 38 publications

(31 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously investigated the in vitro inhibition of CYP3A4 by various commercial herbal tinctures (Budzinski et al, 2000) and numerous other herbal preparations (Foster et al, 2002Awad et al, 2003;Scott et al, 2006), and have made preliminary in vitro investigations of the P-gp ATPase activity and substrate efflux of selected herbals such as garlic, St. John's wort, and African potato (Foster et al, 2001(Foster et al, , 2004Nair et al, 2007). The goal of this study was to determine if selected (Table 1) commercially available teas and capsule preparations of several popular herbal NHPs used by the HIV+ community (CATIE, 2005;Lee et al, 2006), related phytochemicals, and a few HIV drugs could inhibit CYP3A4-mediated metabolism of a reference substrate and stimulate P-gp ATPase activity.…”

Section: Introductionmentioning

confidence: 99%

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

Budzinski

Foster

Trudeau

et al. 2008

Pharmaceutical Biology

Self Cite

View full text Add to dashboard Cite

As the popularity of natural health product (NHP) use increases, unfortunately, so does the frequency of cases reporting suspected adverse interactions. Adverse reactions associated with concomitant NHP-therapeutic use may result from competing interactions at the level of the key xenobiotic-biotransforming phase I enzyme cytochrome P450 3A4 (CYP3A4) or the membrane-bound ATP-dependent protein pump P-glycoprotein (P-gp). In this study, selected NHPs of interest to the HIV+ community were assessed for their ability to affect these two important mechanisms of drug disposition. Briefly, commercial-source teas and powdered extracts in capsule formulations were examined for their ability to inhibit CYP3A4-mediated metabolism of the coadministered reference substrate dibenzyl-fluorescein, and their ability to stimulate P-gp ATPase activity. Among the herbal capsules, it was found that aqueous extracts of two different goldenseal (Hydrastis canadensis L.) products were the most inhibitory of CYP3A4-mediated metabolism among all NHPs tested (IC 50 : 3.03 and 3.23 mg/mL). Goldenseal and milk thistle [Silybum marianum (L.) Gaertn.] teas were found to stimulate P-gp ATPase to a greater degree than the reference positive control verapamil (20 µM). As well, 70% ethanol extracts of one goldenseal product (designated NRP 121) and aqueous extracts of another (designated NRP 17) had the highest relative P-gp ATPase activity overall. Milk thistle and goldenseal products were further analyzed * Dedicated to Professor John Thor Arnason of the University of Ottawa, Department of Biology, on the occasion of his sixtieth birthday.

show abstract

Section: Introductionmentioning

confidence: 99%

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

Budzinski

Foster

Trudeau

et al. 2008

Pharmaceutical Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is prudent to take note of such in vitro interactions as a cautionary signal in the best interests of public health when both ingredients are handled by CYP1A. Clearly, the clinical significance of in vitro interactions needs to be determined by appropriate measures (Nair et al, 2007). The pharmacokinetics and metabolism of DC, DA, and other pyranocoumarins should be investigated to establish their in vivo stability profiles and metabolites.…”

Section: Resultsmentioning

confidence: 99%

In Vitro inhibitory potential of decursin and decursinol angelate on the catalytic activity of cytochrome P-450 1A1/2, 2D15, and 3A12 isoforms in canine hepatic microsomes

et al. 2008

View full text Add to dashboard Cite

Danggui is one of the most popular herbal medicines consumed by patients in different clinical settings in Asian countries. In this study, the two major pyranocoumarin compounds extracted from the Korean Angelica gigas root decursin (DC) and decursinol angelate (DA) were examined in vitro with regard to their abilities to inhibit hepatic CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities in canine liver microsomes. The two components were capable of inhibiting CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities, but the potencies varied. DC and DA selectively and noncompetitively inhibited CYP1A1/2 activity, with K ( i ) values of 90.176 and 67.560 microM, respectively. On the other hand, they exhibited slight inhibitory effects on CYP2D15 and CYP3A12 with K ( i ) values of 666.180 and 872.502 microM, 990.500 and 909.120 microM (1'hydroxymidazolam, MDZ1'H), and 802.800 and 853.920 microM (4-hydroxymidazolam, MDZ4H), respectively. Additionally, they showed increased inhibition after preincubation, which suggests the involvement of a mechanism-based inhibition. In sum, this in vitro data should be heeded as a signal of possible in vivo interactions. The use of human liver preparations would considerably strengthen the practical impact of the data generated from this study.

show abstract

“…Therefore, both rivulobirin A and byakangelicol may strongly inhibit P-gp transport of the concomitantly administered drug. It was also reported that other herbal remedies or phytochemicals inhibited P-gp (Nair et al, 2007;Engdal and Nilsen, 2008). Therefore, it is necessary to investigate the interaction with P-gp between not only Western drugs but also Western drugs and phytochemicals.…”

Section: Tablementioning

confidence: 99%

Furanocoumarin Derivatives in Kampo Extract Medicines Inhibit Cytochrome P450 3A4 and P-Glycoprotein

Iwanaga¹,

Hayashi²,

Hamahata³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Furanocoumarins in grapefruit are known to show inhibitory effects against P-glycoprotein (P-gp) and CYP3A4 in intestinal epithelial cells; however, furanocoumarin derivatives are widely contained in the plants of Rutaceae and Umbelliferae families, which are used as components of Kampo extract medicines. In this study, we investigated the inhibitory effects of 12 furanocoumarins extracted from plants in the Umbelliferae family against P-gp and CYP3A4 activity. Furthermore, we studied their inhibitory effect on P-gp when furanocoumarins are used as Kampo extract medicine rather than as an isolated single compound. From screening of the CYP3A4 inhibitory effect, notopterol and rivulobirin A, the only dimer types of furanocoumarin, were found to be potent inhibitors of CYP3A4. On the other hand, byakangelicol and rivulobirin A showed strong P-gp inhibition from the screening of P-gp inhibitor evaluated by quinidine permeation through the Caco-2 monolayer; however, the chemical structural relationship of furanocoumarins between P-gp and CYP3A4 inhibitory effects could not be obtained. We also investigated the effect of these furanocoumarins on the transport of digoxin through the Caco-2 monolayer. The inhibitory effect of rivulobirin A was more potent than that of byakangelicol. Application of either Senkyu-cha-cho-san or Sokeikakketsu-to, which are composed of herbal remedies in the Umbelliferae group, significantly decreased the efflux ratio of digoxin. In conclusion, it was found that some furanocoumarins extracted from the plants in the Umbelliferae family strongly inhibited P-gp and CYP3A4. Kampo extract medicines containing herbal remedies belonging to the Umbelliferae family may cause a drug-drug interaction with P-gp or a CYP3A4 substrate drug.

show abstract

In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato

Cited by 38 publications

References 38 publications

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

The Interaction of Selected Phytochemicals, HIV Drugs, and Commercial-Source Herbal Teas and Capsules with Human Cytochrome P450 3A4 and P-glycoprotein

In Vitro inhibitory potential of decursin and decursinol angelate on the catalytic activity of cytochrome P-450 1A1/2, 2D15, and 3A12 isoforms in canine hepatic microsomes

Furanocoumarin Derivatives in Kampo Extract Medicines Inhibit Cytochrome P450 3A4 and P-Glycoprotein

Contact Info

Product

Resources

About