CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants

Usia, Tepy; Iwata, Hiroshi; Hiratsuka, Akira; Watabe, Tadashi; Kadota, Shigetoshi; Tezuka, Yasuhiro

doi:10.1016/j.phymed.2004.06.022

Cited by 68 publications

(53 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibitory effects of pepper (Piper nigrum L.) extract and its constituents on CYP3A4 have been reported previously. 7) The IC 50 value for black-pepper extract on CYP3A4-mediated erythromycin metabolism was reported to be 29 mg/ml. Another report demonstrated that alkaloids isolated from white pepper exhibited remarkable inhibition of CYP3A4-mediated nifedipine oxidation with IC 50 values of 0.18-0.79 mM, whereas the main alkaloid piperine showed a moderate inhibition with an IC 50 ϭ12 mM.…”

Section: Resultsmentioning

confidence: 99%

Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity

Kimura

Ito

Hatano

2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity

Kimura

Ito

Hatano

2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

“…, respectively, which should (5) indicate that serpentine (5) was a more potent CYP2D6 inactivator than paroxetine (K I , 4.85 mM; k inact 0.17 min Ϫ1 ) or SCH66712 (K I , 4.8 mM; k inact , 0.14 min Ϫ1 ), other reported mechanism-based inhibitors of CYP2D6 activity. 20,21) To the best of our knowledge, this is the first report of the mechanism-based inhibition of serpentine (5) against CYP2D6.…”

mentioning

confidence: 90%

“…We found that MeOH extracts of Zingiber aromaticum (IC 50 , 102 mg/ml) and Piper cubeba (IC 50 , 53 mg/ ml) showed potent inhibitory activity against CYP3A4, while the MeOH extract of Catharanthus roseus revealed very potent inhibition against CYP2D6 with an IC 50 value of 11 mg/ml. 5) In addition, we reported the CYP3A4 and CYP2D6 inhibitory constituents of Z. aromaticum 6) and P. cubeba.…”

mentioning

confidence: 97%

Cytochrome P450 2D6 (CYP2D6) Inhibitory Constituents of Catharanthus roseus

Usia

Watabe

Kadota

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Herbal medicines are used concomitantly with conventional prescription drugs, which is a situation that carries the risk of unanticipated adverse drug-herbal pharmacokinetic interactions. It is recognized that cytochrome P450 (CYP) enzyme inactivation is one of the main reasons for pharmacokinetic interactions.1,2) The inactivation of CYP can lead to serious clinical drug interactions, especially when concomitant drugs are metabolized by the same enzyme. The drug interactions cause symptoms of drug overdose, including an exaggerated pharmacological response and/or drug toxicity. 3)One of the mechanism of CYP inactivation involves covalent binding of a reactive intermediate to the enzyme proteins and/or heme, which leads to irreversible inhibition of catalytic function, or a quasi-irreversible coordination of a reactive intermediate to the CYP. 4) In Indonesia, herbal medicines "Jamu" have been used from ancient times until the present, and are consumed by people of different levels. Most of these herbal medicines are unregulated, and many patients do not inform their physician of the herbal medicines they consume. Therefore, interactions between herbal medicines and drugs prescribed clinically are becoming a concern. Thus, we investigated in vitro the cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) inhibitory activity of Indonesian medicinal plants. We found that MeOH extracts of Zingiber aromaticum (IC 50 , 102 mg/ml) and Piper cubeba (IC 50 , 53 mg/ ml) showed potent inhibitory activity against CYP3A4, while the MeOH extract of Catharanthus roseus revealed very potent inhibition against CYP2D6 with an IC 50 value of 11 mg/ml.5) In addition, we reported the CYP3A4 and CYP2D6 inhibitory constituents of Z. aromaticum 6) and P. cubeba. 7)Catharanthus roseus, also known as Vinca rosea, is a semiwoody evergreen perennial tree that originated in Madagascar. It has been widely cultivated for hundreds of years and can now be found growing wild in most warm regions of the world. The plant has historically been used to treat a wide assortment of diseases. It was used as a folk remedy for diabetes in Europe for centuries, while in Hawai, the plant was boiled to make a poultice to stop bleeding. In China, it was used as an astringent, diuretic, and cough remedy, and in Central and South America it was used as a homemade cold remedy to ease lung congestion, inflammation, and sore throat. 8) In Indonesia, on the other hand, it was used for treatment of malaria, diabetes, constipation, cancer, and hypertension.9) More than 70 alkaloids were isolated from C. roseus, including vincristine and vinblastine which have anticancer properties.8) Because of continued interest in the CYP study, we carried out phytochemical investigation of C. roseus from Indonesia. In this paper, we report the constituents of this plant and their inhibitory activity on the metabolism mediated by CYP3A4 and CYP2D6. We also examined the possibility of mechanism-based inhibition by these constituents. MATERIALS AND METHODS Extraction and IsolationThe aerial...

show abstract

“…Besides the alteration of their own activity after metabolism (Cech et al, 2006), NAA containing plants (like Echinacea spp., Heliopsis spp., Piper spp., Capsicum spp.) and isolated NAAs with a terminal alkyne group inhibit P450 enzymes Pandit et al, 2012;Rodeiro et al, 2009;Subehan et al, 2006;Usia et al, 2006) and hence can also influence the metabolism of other drugs. Nevertheless, in-vitro as well as in-vivo studies showed this herb-drug interaction is clinically not significant (Toselli et al, 2009).…”

Section: Pk/pd Interactionsmentioning

confidence: 99%

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

Boonen

Bronselaer

Nielandt

et al. 2012

Journal of Ethnopharmacology

137

109

View full text Add to dashboard Cite

a b s t r a c tEthnopharmacological relevance: N-Alkylamides (NAAs) are a promising group of bioactive compounds, which are anticipated to act as important lead compounds for plant protection and biocidal products, functional food, cosmeceuticals and drugs in the next decennia. These molecules, currently found in more than 25 plant families and with a wide structural diversity, exert a variety of biologicalpharmacological effects and are of high ethnopharmacological importance. However, information is scattered in literature, with different, often unstandardized, pharmacological methodologies being used. Therefore, a comprehensive NAA database (acronym: Alkamid) was constructed to collect the available structural and functional NAA data, linked to their occurrence in plants (family, tribe, species, genus). Materials and methods: For loading information in the database, literature data was gathered over the period 1950-2010, by using several search engines. In order to represent the collected information about NAAs, the plants in which they occur and the functionalities for which they have been examined, a relational database is constructed and implemented on a MySQL back-end. Results: The database is supported by describing the NAA plant-, functional-and chemical-space. The chemical space includes a NAA classification, according to their fatty acid and amine structures. Conclusions: The Alkamid database (publicly available on the website http://alkamid.ugent.be/) is not only a central information point, but can also function as a useful tool to prioritize the NAA Q8 choice in the evaluation of their functionality, to perform data mining leading to quantitative structure-property relationships (QSPRs), functionality comparisons, clustering, plant biochemistry and taxonomic evaluations.

show abstract

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants

Cited by 68 publications

References 14 publications

Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity

Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity

Cytochrome P450 2D6 (CYP2D6) Inhibitory Constituents of Catharanthus roseus

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

Contact Info

Product

Resources

About