Buradasınız

Anasayfa » Content

SCREENING OF SOME SELECTED PLANTS FOR CYP3A INHIBITION AND BIOAVAILABILITY ENHANCEMENT

Journal Name:

  • Advance Research in Pharmaceuticals and Biologicals

Publication Year:

  • 2011

Key Words:

Author Name
Abstract (2. Language): 
Herbals and other natural remedies could affect the disposition of conventional pharmaceuticals through inhibition of human cytochrome P-450 (CYP) enzymes. The inhibitory effect of five selected plants extracts on cytochrome P450 3A were investigated using rat liver microsomes. The methanol soluble fractions of five selected plant samples, prepared from methanolic extracts, demonstrated inhibitory activity of CYP3A enzyme by using in vitro assay, erythromycin n-demethylation (EMD). Among these five plants Daucus carota (Carrot), Embilica officinale (Amla) and Zingiber officinale (Ginger), and ketoconazole (10 mM) (positive control) have shown CYP3A inhibitory activity 669.33 ± 11.135, 868.33 ± 14.107, 484.00 ± 9.292 and 349.67 ± 7.00 nM/mg protein per min, respectively. In another experiment, erythromycin estolate was administered orally (50 mg/kg) to active ginger extract (200 mg/kg) pretreated male rats and its plasma levels were determined at various time points (0.5, 1, 2, 4, 8 and 24 h after oral administration by HPLC. Active ginger extract pretreatment increased AUC0–∞ of erythromycin estolate after oral administration by 6%, suggesting decreased metabolism, which could be due to inhibition of CYP3A by ginger extract. In conclusion, add-on preparations containing ginger may increase the bioavailability of erythromycin, and hence should be cautiously used.
Bookmark/Search this post with
FULL TEXT (PDF): 
PDF icon arastrmx_160852_1_pp_19-27.pdf
  • 1
19-27
  • English

REFERENCES

References: 

1. S. Rendic, F. Di Carlo. Human
cytochrome P450 enzymes: a status
report summarizing their reactions,
substrates, inducers, and inhibitor,
Drug Metab Rev 29: 413–580 (1997)
2. R. J. Bertz, G. R. Granneman. Use of
in vitro and in vivo data to estimate the
likelihood of metabolic
pharmacokinetic interactions, Clin.
Pharmacokinet 32: 210–58 (1997).
3. J. A. Hasler, R. Estabrook, M. Murray,
I. Pikuleva, M. Waterman, et al.
Human cytochromes P450, Mol. Asp.
Med, 20, 1-137 (1999).
4. T. Usia, H. Iwata, A. Hiratsuka, T.
Watabe, S. Kadota, Y. Tezuka.
CYP3A4 and CYP2D6 inhibitory
activities of Indonesian medicinal
plants, Phytomedicine 13: 67–73
(2006).
5. Z. Q. Wang, C. Gorski, M. A.
Hamman, S. M. Huang, L. J. Lesko, S.
D. Hall. The effects of St. John’s wort
(Hypericum perforatum) on human
cytochrome P450 activity, Clin.
Pharmacol. Ther, 70, 317–26 (2001).
6. B. Ameer, R. A. Weintraub. Drug
interactions with grapefruit juice, Clin.
Pharmacokinet, 33, 103–21 (1997).
7. D. G. Bailey, J. Malcolm, O. Arnold, J.
D. Spence. Grapefruit juice–drug
interactions, Br. J. Clin. Pharmacol, 46,
101–10 (1998).
8. S. Kanazawa, T. Ohkubo, K.
Sugawara. The effects of grapefruit
juice on the pharmacokinetics of
erythromycin, Eur. J. Clin. Pharmacol,
56: 799-803 (2001).
9. R. J. Riley, D. Howbrook. In vitro
Analysis of the Activity of the Major
Human Hepatic CYP Enzyme
(CYP3A4) Using [N-Methyl-14C] –
Erythromycin, J. Pharmacol. Toxicol.
Met. 38: 189-93 (1998)
10. J. G. Sarver. Ethosuximide is primarily
metabolized by CYP3A when
incubated with isolated rat liver
microsomes, Drug Met Dispos 26: 78-
82 (1996).
11. S. N. Umathe, P. V. Dixit, V. Kumar,
K. U. Bansod, M. M. Wanjari.
Quercetin pretreatment increases the
bioavailability of pioglitazone in rats:
Involvement of CYP3A inhibition,
Biochem. Pharmaco, l75: 1670-76
( 2008).
12. O. H. Lowry, N. J. Rosebrough, A. L.
Farr, R. J. Randall. Protein
measurement with the Folin phenol
reagent, J. Bio Chem, 193: 265–75
(1951).
13. W. Xiao, B. Chen, S. Yao, Z. Cheng.
Simultaneous determination of
erythromycin propionate and base in
human plasma by liquid
chromatography-electronspray mass
spectrometry, J. Chomatogr, 817: 153-
58 (2005).
14. L. Shargel, A. B. Yu. Applied
biopharmaceutics & pharmacokinetics.
McGraw-Hill, New York, 35-120
(1999).
15. T. Shimada, H. Yamazaki, M. Mimura,
Y. Inui, F.P. Guengerich.
Interindividual variations in human
liver cytochrome P450 enzymes
involved in the oxidation of drugs,
carcinogens, and toxic chemicals, J.
Pharmacol. Exp, 270: 414–23 (1994).
Maitreyi Zaveri, et al., ARPB, 2011; Vol 1(1) ISSN 2250 - 0774
(Research paper)
www.arpb.info Page 27
16. S. Zhou, Y. Gao, W. Jiang, M. Huang,
A. Xu, J.W. Paxton. Interactions of
Herbs with Cytochrome P450, Drug
Met. Rev, 35: 95–98 (2003).
17. T. Winitthana, M. Tantisira, N.
Niwattisaiwong, S. Lawanprasert.
Effects of asiaticoside and
madecassoside on human cytochrome
P450, Thai J. Pharmacol, 31: 111-14
(2009).
18. K. Kim, J. Lee, H. Park, J. Kim, C.
Kim. Inhibition of cytochrome P450
activities by oleanolic acid and ursolic
acid in human liver microsomes, Life
Sciences 74: 2769–79 (2004).

Thank you for copying data from http://www.arastirmax.com