Inhibitory Effects of Kampo Medicine on Human UGT2B7 Activity

Nakagawa, Nao; Katoh, Miki; Yoshioka, Yoshiaki; Nakajima, Miki; Yokoi, Tsuyoshi

doi:10.2133/dmpk.24.490

Cited by 10 publications

(2 citation statements)

References 36 publications

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“…But two studies showed that there was wide variability in affinity for UDP-glucuronosyltransferase (UGT) and sulfotransferase (ST) across both general classes of substrates (Chen et al, 1996; Ebner and Burchell, 1993). One related triterpenoid, glycyrrhetinic acid (50-300 μM), was found to inhibit UGT2B7 activity in human liver microsomes (Nakagawa et al, 2009), which might also occur for UA. To our knowledge, no other in vivo or in vitro study has been done on the metabolism of ursolic acid.…”

Section: Discussionmentioning

confidence: 99%

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

Qiang

Hauck

et al. 2011

Journal of Ethnopharmacology

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Ethnopharmacological relevance Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. Aim of the study To investigate the permeabilities of RA and UA as pure compounds and in P. vulgaris and S. officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. Materials and methods The permeabilities and Phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. Results The apparent permeability coefficient (Papp) for RA and RA in P. vulgaris extracts was 0.2 ± 0.05 × 10−6 cm/s, significantly increased to 0.9 ± 0.2 × 10−6 cm/s after β-glucuronidase/sulfatase treatment. Papp for UA and UA in S. officinalis extract was 2.7 ± 0.3 × 10−6 cm/s and 2.3 ± 0.5 × 10−6 cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. Conclusion RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA.

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Section: Discussionmentioning

confidence: 99%

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

Qiang

Hauck

et al. 2011

Journal of Ethnopharmacology

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“…Kampo, a traditional Japanese medicine made of a mixture of several medicinal herbs has shown inhibitory effects on some phase II enzymes. In an in vitro study by Nakagawa et al (2009), nine out of 51components of kampo medicine elicited more than 50% inhibition of UGT2B7-mediated morphine 3-glucuronidation. In the same study, extracts of kanzo ( Glycyrrhizae radix ), daio ( Rhei rhizoma ), and keihi ( Cinnamomi cortex ) elicited more than 80% inhibition of morphine AZT glucuronidation.…”

Section: Resultsmentioning

confidence: 99%

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

Fasinu¹,

Bouic²,

Rosenkranz³

2012

Front. Pharmacol.

205

140

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Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complementary medicine is globally popular. There is also an increasing interest in medicinal herbs as precursor for pharmacological actives. Of serious concern is the concurrent consumption of herbal products and conventional drugs. Herb–drug interaction (HDI) is the single most important clinical consequence 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 and transport proteins; and alteration of renal excretion of drugs and their metabolites. 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 the inability to promptly identify HDI by health providers are identified as major factors limiting the extensive compilation of clinically relevant HDIs. A general overview and the significance of pharmacokinetic and pharmacodynamic HDI are provided, detailing basic mechanism, and nature of evidence available. An increased level of awareness of HDI is necessary among health professionals and drug discovery scientists. With the increasing number of plant-sourced pharmacological actives, the potential for HDI should always be assessed in the non-clinical safety assessment phase of drug development process. More clinically relevant research is also required in this area as current information on HDI is insufficient for clinical applications.

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UDP‐Glucuronosyltransferases: Pharmacogenetics, Functional Characterization, and Clinical Relevance

Foti

Fisher

2012

Encyclopedia of Drug Metabolism and Interactions

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UDP‐glucuronosyltransferase (UGT)‐catalyzed conjugation reactions play an important role in the metabolism of both xenobiotics and endogenous compounds. The frequency of UGT involvement in xenobiotic drug metabolism has increased as the ability to design out other routes of metabolism (i.e., cytochrome P450) has improved. To this end, the primary goal of this chapter is to serve as a compendium for the significant amount of information surrounding UGTs that has been compiled to date. Where relevant, the chapter covers expression, regulation and polymorphisms, substrates and inhibitors, active site characterization, and finally, clinical relevance of the various UGT isoforms.

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Inhibitory Effects of Kampo Medicine on Human UGT2B7 Activity

Cited by 10 publications

References 36 publications

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

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

UDP‐Glucuronosyltransferases: Pharmacogenetics, Functional Characterization, and Clinical Relevance

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