Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat

Mitragynine is a major indole alkaloid abundantly isolated from M. speciosa leaves. Mitragynine exhibits psychoactive properties and shows morphine-like depressant effect and cocaine-like stimulant effects. Mitragynine also shows antitussive and antidepressant-like effects. The current research was...

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Main Author:	Anwar, Rukhsana
Format:	Thesis
Language:	English
Published:	2013
Subjects:	R5-920 Medicine (General)
Online Access:	http://eprints.usm.my/44466/1/Rukhsana%20Anwar-24.pdf
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spelling	my-usm-ep.444662019-05-31T00:35:33Z Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat 2013-08 Anwar, Rukhsana R5-920 Medicine (General) Mitragynine is a major indole alkaloid abundantly isolated from M. speciosa leaves. Mitragynine exhibits psychoactive properties and shows morphine-like depressant effect and cocaine-like stimulant effects. Mitragynine also shows antitussive and antidepressant-like effects. The current research was undertaken to evaluate the in vitro and in vivo effect of mitragynine on phase I and phase II drug metabolizing enzymes, namely aminopyrine N-demethylase (APND), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) in normal and diabetes Sprague-Dawley (SD) rat liver. The in vitro effect of mitragynine on APND activity in relation to factors of age, gender and diabetes was determined in rat hepatocytes. Moreover, the possible mechanism of induction of aminopyrine N-demethylase activity by mitragynine was also investigated in SD rat hepatocytes. In addition, western blot analysis was carried out for in vivo CYP2C12 and UGT1A6 and GSTM1 proteins expression in normal and diabetic rats. Aminopyrine, p-nitrophenol and 1-chloro-2,4-dinitro benzene were used as a probes to determine the APND, UGT and GST activity respectively. A range of mitragynine concentration (0.0025 – 250 μM) was used for all in vitro enzyme assays in tested groups of SD rats. The mitragynine 50 mg/kg of body weight was administered orally to SD rats for in vivo study. Results of in vitro study showed that mitragynine significantly (p < 0.05) enhanced APND activity in rat hepatocytes as well as significantly inhibited microsomal UGT and cytosolic GST activity in normal and diabetic 2013-08 Thesis http://eprints.usm.my/44466/ http://eprints.usm.my/44466/1/Rukhsana%20Anwar-24.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Penyelidikan Dadah dan Ubat-Ubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R5-920 Medicine (General)
spellingShingle	R5-920 Medicine (General) Anwar, Rukhsana Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
description	Mitragynine is a major indole alkaloid abundantly isolated from M. speciosa leaves. Mitragynine exhibits psychoactive properties and shows morphine-like depressant effect and cocaine-like stimulant effects. Mitragynine also shows antitussive and antidepressant-like effects. The current research was undertaken to evaluate the in vitro and in vivo effect of mitragynine on phase I and phase II drug metabolizing enzymes, namely aminopyrine N-demethylase (APND), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) in normal and diabetes Sprague-Dawley (SD) rat liver. The in vitro effect of mitragynine on APND activity in relation to factors of age, gender and diabetes was determined in rat hepatocytes. Moreover, the possible mechanism of induction of aminopyrine N-demethylase activity by mitragynine was also investigated in SD rat hepatocytes. In addition, western blot analysis was carried out for in vivo CYP2C12 and UGT1A6 and GSTM1 proteins expression in normal and diabetic rats. Aminopyrine, p-nitrophenol and 1-chloro-2,4-dinitro benzene were used as a probes to determine the APND, UGT and GST activity respectively. A range of mitragynine concentration (0.0025 – 250 μM) was used for all in vitro enzyme assays in tested groups of SD rats. The mitragynine 50 mg/kg of body weight was administered orally to SD rats for in vivo study. Results of in vitro study showed that mitragynine significantly (p < 0.05) enhanced APND activity in rat hepatocytes as well as significantly inhibited microsomal UGT and cytosolic GST activity in normal and diabetic
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Anwar, Rukhsana
author_facet	Anwar, Rukhsana
author_sort	Anwar, Rukhsana
title	Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
title_short	Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
title_full	Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
title_fullStr	Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
title_full_unstemmed	Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat
title_sort	phase i and phase ii drug metabolism study of mitragynine in normal and diabetes induced rat
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Penyelidikan Dadah dan Ubat-Ubatan
publishDate	2013
url	http://eprints.usm.my/44466/1/Rukhsana%20Anwar-24.pdf
_version_	1747821375794446336

Phase I And Phase Ii Drug Metabolism Study Of Mitragynine In Normal And Diabetes Induced Rat

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