Alleviating Effect of Mitragynine on Microsomal UDP-Glucuronosyltransferase Activity and UGT1A6 Expression in STZ-Induced Diabetic Rat
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1
University of the Punjab, Punjab University College of Pharmacy, Pakistan
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2
University of Science, Malaysia, Centre for Drug Research, Malaysia
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3
Center for drug research, University of Science, Malaysia, Malaysia
Abstract
Background
Mitragyna speciosa (MS) Korth is a member of the Rubiaceae family, found in Peninsular Malaysia and Thailand. MS leaves are being used for opium withdrawal, as analgesic and to treat diarrhea. Mitragynine (MTG) is a major indole alkaloid of MS leaves. Its analgesic, antipyretic and behavioral effects have been studied. Efficacy and safety are essential parameters during herbal derived drug development. It is only possible by evaluation of types of enzymes involved in its metabolism. Till now, no in vivo study has been done about the effect of mitragynine on UDP-glucuronosyltransferase (UGT) phase II drug metabolizing enzyme activity. Herbal derived compounds modulate the expression of hepatic enzymes that is an important mechanism determines the bioavailability of co-administered drug.
Methods
The following research was undertaken to investigate effect of MTG on UGT activity in healthy and diabetic male Sprague Dawley (SD) rats. Diabetes was induced by streptozotocin. For sub-acute in vivo study, 50 mg/ kg mitragynine (single oral daily dose for 14 days) administered to healthy and diabetic rats. Pooled liver microsomes were prepared by differential centrifugation technique. The p-nitrophenol was used as a probe substrate for estimation of UGT activity in rat liver microsomes. Effect of MTG on the UGT1A6 protein expression rat liver microsomes were measured in three independent immunobloting assays. The protein band was quantified by densitometry and the level of control was set at 1.
Results
The sub-acute administration of mitragynine to normal male rats showed significant (p < 0.05) 189% increase in UGT specific activity and diabetic rats showed 172% induction in UGT specific activity as compared to respective control group. The fold change in UGT1A6 protein expression in both groups was more than 2-fold indicating that MTG was a significant UGT1A6 inducer.
Conclusion
Mitragynine significantly induced activity of UGT & expression of UGT1A6 in normal and diabetic rats.
Acknowledgements
The author would like to acknowledge University of the Punjab Lahore, Pakistan for grant of PhD scholarship.
Keywords:
UGT,
mitragynine,
Microsomes,
UGT1A6,
Immunobloting
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Poster Presentation
Topic:
Miscellaneous
Citation:
Anwar
R,
Ismail
S,
Mansur
SM and
Lan
TM
(2019). Alleviating Effect of Mitragynine on Microsomal UDP-Glucuronosyltransferase Activity and UGT1A6 Expression in STZ-Induced Diabetic Rat.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00045
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Received:
27 Sep 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Rukhsana Anwar, University of the Punjab, Punjab University College of Pharmacy, Lahore, Punjab, 46000, Pakistan, rukhsana.pharmacy@pu.edu.pk