Effect of Morinda Citrifolia (LINN.) on phase I and II drug metabolism and its molecular mechanism elucidation in rat liver
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Date
2006
Authors
Al-Musli Mohammed, Mahfoudh
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Abstract
Morinda 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.
Description
PhD
Keywords
Pharmaceutical science , Morinda Citrifolia (LINN.) , Drug metabolism , Rat liver