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Interactions between CYP3A4 and Dietary Polyphenols.

Basheer L, Kerem Z - Oxid Med Cell Longev (2015)

Bottom Line: Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs.Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4.Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, 76100 Rehovot, Israel.

ABSTRACT
The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.

No MeSH data available.


Related in: MedlinePlus

Classification of polyphenols.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig2: Classification of polyphenols.

Mentions: As reviewed in other works in this issue, polyphenols constitute a large and diverse family of compounds that is commonly divided into subfamilies that share similar chemistry: flavonoids, flavonols, phenolic acids, phenolic alcohols, stilbenoids, tannins, and lignans (Figure 2). Polyphenols are found in several foods, fruits, vegetables, and herbs [52, 94, 95]. In general, the total intake of polyphenols is approximated at 1 g/individual/day and polyphenols are considered by many to be the major source of antioxidants in our diet [51, 95–97]. However, this estimate varies depending on the type of diet. For example, total polyphenol intake in the Finnish diet is 817–919 mg/individual/day [98]. In the Vietnamese diet, it is 595 mg/individual/day [99], and in the Mediterranean diet, polyphenol intake ranges between 1800 and 3000 mg/individual/day [100]. Still, and due to their low absorption, it has been suggested that their major sites of antioxidant activity are the stomach [101] and the intestine [102]. Whether acting in the gastrointestinal tract or in the liver, the potent antioxidant effects of polyphenols are widely accepted as health promoting [103–105]. Antivira, antibacterial, anti-inflammatory, neuroprotective, and anticarcinogenic effects have also been attributed to polyphenols [106–109]. Medicinal herbs such as St. John's wort (Hypericum perforatum), ginseng (Panax ginseng), black cohosh (Actaea racemosa), echinacea (Echinacea purpurea), cranberry (Vaccinium macrocarpon), and ginger (Zingiber officinale) are rich sources of a vast array of polyphenolic compounds [74, 110–115]. The biochemical mechanisms underlying metabolic herb-drug interaction were well described in a recent review [72]. These herbal sources of polyphenols deserve special attention when the activity of P450s is discussed, due to the dramatic increase in the use of herbal medicines and supplements [65, 66]. Recent surveys suggest that one in three Americans use dietary supplements daily and among cancer patients the rate is much higher [54]. Moreover, medicinal herbs are not inspected by regulatory authorities such as the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) [72]. Indeed, medical doctors as well as pharma professionals should be aware of the many interactions of polyphenolics with drugs and tools should be developed to assess the potential of individual polyphenolics to enter the active sites of P450 enzymes and become substrates, competitive inhibitors, or other types of inhibitors of these enzymes in the intestine and the liver. CYP3A4 should be a major point of focus in studies of the undesirable clinical consequences of the timed use of prescribed drugs and herbs [74].


Interactions between CYP3A4 and Dietary Polyphenols.

Basheer L, Kerem Z - Oxid Med Cell Longev (2015)

Classification of polyphenols.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4477257&req=5

fig2: Classification of polyphenols.
Mentions: As reviewed in other works in this issue, polyphenols constitute a large and diverse family of compounds that is commonly divided into subfamilies that share similar chemistry: flavonoids, flavonols, phenolic acids, phenolic alcohols, stilbenoids, tannins, and lignans (Figure 2). Polyphenols are found in several foods, fruits, vegetables, and herbs [52, 94, 95]. In general, the total intake of polyphenols is approximated at 1 g/individual/day and polyphenols are considered by many to be the major source of antioxidants in our diet [51, 95–97]. However, this estimate varies depending on the type of diet. For example, total polyphenol intake in the Finnish diet is 817–919 mg/individual/day [98]. In the Vietnamese diet, it is 595 mg/individual/day [99], and in the Mediterranean diet, polyphenol intake ranges between 1800 and 3000 mg/individual/day [100]. Still, and due to their low absorption, it has been suggested that their major sites of antioxidant activity are the stomach [101] and the intestine [102]. Whether acting in the gastrointestinal tract or in the liver, the potent antioxidant effects of polyphenols are widely accepted as health promoting [103–105]. Antivira, antibacterial, anti-inflammatory, neuroprotective, and anticarcinogenic effects have also been attributed to polyphenols [106–109]. Medicinal herbs such as St. John's wort (Hypericum perforatum), ginseng (Panax ginseng), black cohosh (Actaea racemosa), echinacea (Echinacea purpurea), cranberry (Vaccinium macrocarpon), and ginger (Zingiber officinale) are rich sources of a vast array of polyphenolic compounds [74, 110–115]. The biochemical mechanisms underlying metabolic herb-drug interaction were well described in a recent review [72]. These herbal sources of polyphenols deserve special attention when the activity of P450s is discussed, due to the dramatic increase in the use of herbal medicines and supplements [65, 66]. Recent surveys suggest that one in three Americans use dietary supplements daily and among cancer patients the rate is much higher [54]. Moreover, medicinal herbs are not inspected by regulatory authorities such as the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) [72]. Indeed, medical doctors as well as pharma professionals should be aware of the many interactions of polyphenolics with drugs and tools should be developed to assess the potential of individual polyphenolics to enter the active sites of P450 enzymes and become substrates, competitive inhibitors, or other types of inhibitors of these enzymes in the intestine and the liver. CYP3A4 should be a major point of focus in studies of the undesirable clinical consequences of the timed use of prescribed drugs and herbs [74].

Bottom Line: Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs.Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4.Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, 76100 Rehovot, Israel.

ABSTRACT
The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.

No MeSH data available.


Related in: MedlinePlus