Effect of Morinda Citrifolia (LINN.) on phase I and II drug metabolism and its molecular mechanism elucidation in rat liver

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dc.contributor.authorAl-Musli Mohammed, Mahfoudh
dc.date.accessioned2014-11-03T02:27:22Z
dc.date.available2014-11-03T02:27:22Z
dc.date.issued2006
dc.descriptionPhDen_US
dc.description.abstractMorinda citrifolia commonly known as Noni and locally known as mengkudu is one of the most important traditional Polynesian medicinal plants. Morinda citrifolia (Noni) has been used extensively in folk medicine by Polynesians for over 2,000 years. It has been reported to have broad therapeutic effects, including anticancer properties in clinical practice and in laboratory animal models and are effective as antibacterial, antiviral, antifungal, antihelminthics, analgesic, hypotensive, anti-inflammatory agents, and immune system enhancing effects. As the use of phytomedicine together with modern medications has become more popular nowadays, the possibilities of herbdrug interactions have increased. Little is known about the incidence and consequences of herb-drug interactions in patients receiving herbal product of mengkudu juice. The aims of the study were to investigate, primarily, the in-vitro effect of Morinda citrifolia on phase I and II metabolizing enzymes in rat liver; the influence of diseases (diabetes and hypertension), gender and age on the foregoing effect, as well as to elucidate the molecular mechanism of M. citrifolia effect on aminopyrine phase I metabolism. Our in-vitro study showed that effect of mengkudu juice extract (MJE), Hawaiian Noni juice (HNJ) and Tahiti Noni juice (TNJ) of M. citrifolia increased aminopyrine metabolism especially at high concentrations in normal rat (NR), diabetic rat (DR) and spontaneously hypertensive rats (SHR). This study shows that, diabetes and gender differences have significantly influenced the in-vitro effects of M. citrifolia on liver aminopyrine metabolism. In acute study (one day) of orally administrated MJE, the aminopyrine N-demethylase activity was significantly increased at the highest dose level (210 mg/kg) while the activity of glutathione S-transferase (GST) was significantly increased at 2.1, 21 and 210 mg/kg concentrations. However, in the sub-chronic study, uridine diphosphate glucuronosyltransferase (UDP-GT) activity was significantly decreased but was dose independent while aminopyrine N-demethylase activity was not changed. A possibility exist that similar interactions may occur in-vitro and ex-vivo with other drugs that undergo the same hepatic phase I N-demethylation and/or hepatic phase II conjugations. Whether this effect is similarly produced in-vivo still needs further investigation. The molecular mechanism study suggests that protein kinase A may be involved in the molecular mechanism of MJE acute effect on aminopyrine metabolism in young female SHR. Qualitative screening using IR, 1HNMR spectroscopies and HPTLC showed that the tested samples of M. citrifolia have qualitative similarities in their major constituents. The characteristics of these constituents mostly resemble the functional groups of anthraquinones, sterols, glycoside and flavonol compounds which have been reported by several authors.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/313
dc.language.isoenen_US
dc.subjectPharmaceutical scienceen_US
dc.subjectMorinda Citrifolia (LINN.)en_US
dc.subjectDrug metabolismen_US
dc.subjectRat liveren_US
dc.titleEffect of Morinda Citrifolia (LINN.) on phase I and II drug metabolism and its molecular mechanism elucidation in rat liveren_US
dc.typeThesisen_US
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