Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complimentary medicine is globally popular. There is also increasing interest in medicinal herbs as precursor of pharmacological actives. Of serious concern is their concurrent consumption with conventional drugs. Herb-drug interaction (HDI) is the single most important clinical consequences of this practice. Using a structured assessment procedure, the evidence of HDI presents with varying degree of clinical significance. While the potential for HDI for a number of herbal products is inferred from non-human studies, certain HDIs are well established through human studies and documented case reports. Various mechanisms of pharmacokinetic HDI have been identified and include the alteration in the gastrointestinal functions with consequent effects on drug absorption; induction and inhibition of metabolic enzymes; the induction and inhibition of transport proteins and stimulation of changes to hepatic and renal functions leading to alteration in drug elimination profiles. Due to the intrinsic pharmacologic properties of phytochemicals, pharmacodynamic HDIs are also known to occur. The effects could be synergistic, additive and/or antagonistic. Poor reporting on the part of patients and inability to promptly identify HDI by health providers are identified as major factors in compiling clinically relevant HDIs. A general overview and the significance of pharmacokinetic and pharmacodynamic HDI are provided, detailing basic mechanism and nature of evidence available. The potential of new chemical entities to be involved in HDIs should be considered in their non-clinical safety assessment during the drug development process. More clinically relevant research is also required in this area as current information on HDI is insufficient for clinical applications to increase the level of awareness among health professionals.

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An Overview of the Evidence and Mechanisms of Herb–Drug Interactions

Herbal interactions on absorption of drugs: Mechanisms of action and clinical risk assessment.

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.

/pdf/interactions-between-cyp3a4-and-dietary-polyphenols-4zdmc3cg0u.pdf

Interactions between CYP3A4 and Dietary Polyphenols

An extract of black, green, and mulberry teas causes malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers

The concurrent use of drugs and herbal products is becoming increasingly prevalent over the last decade. Several herbal products have been known to modulate cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) which are recognized as representative drug metabolizing enzymes and drug transporter, respectively. Thus, a summary of knowledge on the modulation of CYP and P-gp by commonly used herbs can provide robust fundamentals for optimizing CYP and/or P-gp substrate drug-based therapy. Herein, we review ten popular medicinal and/or dietary herbs as perpetrators of CYP- and P-gp-mediated pharmacokinetic herb-drug interactions. The main focus is placed on previous works on the ability of herbal extracts and their phytochemicals to modulate the expression and function of CYP and P-gp in several in vitro and in vivo animal and human systems.

https://downloads.hindawi.com/journals/ecam/2015/736431.pdf

Nobuhito Kimura

Papers

Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam.