Publications by authors named "Yasotha Devi Muthiah"

2 Publications

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Inhibition of Human Cytochrome P450 2c8-catalyzed Amodiaquine N-desethylation: Effect of Five Traditionally and Commonly Used Herbs.

Pharmacognosy Res 2016 Oct-Dec;8(4):292-297

Centre of Excellence for Research in AIDS, Universiti Malaya, 59990 Kuala Lumpur, Malaysia.

Background: In Southeast Asia and many parts of the world, herbal products are increasingly used in parallel with modern medicine.

Objective: This study aimed to investigate the effects of herbs commonly used in Southeast Asia on activity of cytochrome P450 2C8 (CYP2C8), an important human hepatic enzyme in drug metabolism.

Materials And Methods: The selected herbs, such as Jack (ELJ), (LP), (EP), (AP), and (GB), were subjected to inhibition studies using an CYP2C8 activity marker, amodiaquine N-desethylase assay. Inhibition parameters, inhibitory concentration 50% (IC), and K values were determined to study the potency and mode of inhibition.

Results: All herbs inhibited CYP2C8 with the following order of potency: LP > ELJ > GB > AP > EP. LP and ELJ inhibited potently at K's of 2 and 4 times the K of quercetin, the positive control. The inhibition by LP was uncompetitive in nature as compared to competitive or mixed type inhibition observed with other herbs. GB exhibited moderate inhibitory effect at a K6 times larger than quercetin K. AP and EP, on the other hand, showed only weak inhibition.

Conclusion: The herbs we chose represented the more commonly used herbs in Southeast Asia where collision of tradition and modernization in healthcare, if not properly managed, may lead to therapeutic misadventures. We conclude that concurrent consumption of some herbs, in particular, LP and ELJ, may have relevance in drug-herb interactions via CYP2C8 inhibition .

Summary: Herbs are increasingly used in parallel with modern medicines nowadays. In this study five commonly used herbs in Southeast Asia region, ELJ, LP, EP, AP and GB, were investigated for their inhibitory potency on CYP2C8, an important drug-metaboliz-ing human hepatic enzyme. All herbs inhibited CYP2C8 activity marker, amodiaquine N-desethylation, with potency order of LP > ELJ > GB >AP > EP. LP, ELJ and GB exhibited K values of 2, 4 and 6 times the K of quercetin, the positive control, indicating potent to moderate degree of enzyme inhibition. AP and EP, on the other hand, showed only weak inhibition. In summary, concurrent consumption of some herbs especially LP and ELJ may have relevance in drug-herb interactions via CYP2C8 inhibition . : AQ: Amodiaquine, AP: , CYP: Cytochrome P450, DEAQ: Desethylamodiaquine, EP: , ELJ: , GB: , K: Inhibition constant, LP: , Vmax: Maximal velocity, K: Michaelis-Menten constant.
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http://dx.doi.org/10.4103/0974-8490.188886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004522PMC
October 2016

In-vitro inhibitory effect of Tualang honey on cytochrome P450 2C8 activity.

J Pharm Pharmacol 2012 Dec 8;64(12):1761-9. Epub 2012 Jun 8.

Pharmacogenetics & Novel Therapeutics Cluster, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.

Objectives: To investigate the effect of Tualang honey on cytochrome P450 2C8 (CYP2C8) activity in vitro using an amodiaquine N-desethylase assay.

Methods: CYP2C8 and NADPH cytochrome P450 reductase was cotransformed, expressed and harvested. The incubation assay contained expressed proteins, MgCl(2), NADP, glucose 6-phosphate, glucose-6-phosphate dehydrogenase, potassium phosphate buffer, and amodiaquine. The rate of conversion of amodiaquine to desethylamodiaquine, the metabolite, was determined using a high performance liquid chromatography (HPLC) method. The inhibition parameters, IC50 (concentration of inhibitor causing 50% inhibition of original enzyme activity) and apparent inhibition constant (K(i) ) values were determined.

Key Findings: The recombinant proteins were successfully expressed and used to investigate the effect of Tualang honey on CYP2C8 activity. The activity was measured by the rate of metabolism of amodiaquine to desethylamodiaquine determined using a successfully developed HPLC method. Kinetic parameters as determined by nonlinear least-squares regression and evaluated with Aikeike's goodness of fit criteria revealed that Tualang honey competitively inhibited CYP2C8 activity in a dose-dependent manner. Maximum inhibition of 80% occurred at 0.01% honey. The IC50 and K(i) values were (10.0 ± 3.0) × 10(-3) % and (5.1 ± 0.5) × 10(-3) % w/v, respectively.

Conclusions: This study has provided evidence for the in vitro inhibition of CYP2C8-mediated amodiaquine N-desethylase activity by Tualang honey. It revealed that honey, through this inhibition, may have the potential to cause in-vivo drug-food interaction with drugs metabolized by CYP2C8.
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http://dx.doi.org/10.1111/j.2042-7158.2012.01551.xDOI Listing
December 2012