Drug metabolism and toxicity studies of orthosiphon stamineus, benth (misai kucing) in rats
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Date
2006
Authors
Jin Han, Chin
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Abstract
Orthosiphon stamineus, Benth (Family: Lamiaceae) or locally known as Misai
Kucing, is widely used in Malaysia for treating hypertension, urinary system ailments
and kidney stone disease. The objective of this study is to investigate the effect of
standardised methanol extract of Misai Kucing on phase I and phase II hepatic drug
metabolising enzymes in Sprague-Oawley (SO) rat. Aminopyrine, p-nitrophenol (pNP)
and 1-chloro-2,4-dinitro benzene (CONB) was used as a substrate to determine the
aminopyrine N-demethylase, UOP-glucuronosyltransferase (UGT) and glutathione-Stransferase
(GST) activity respectively in SD rat liver. Isolated hepatocytes, liver
cytosolic fraction and liver microsomes from SO rats were prepared using the
collagenase perfusion technique and differential centrifugation technique. The possible
toxic and anti-hepatotoxicity effects of standardised of methanol extract of Misai Kucing
on SO rats were also examined. Results obtained showed that most of the UGT and
GST activity in normal and diabetic SO rat liver were significantly affected by
standardised methanol extract of Misai Kucing. Only a few groups of normal and
diabetic SO rats showed significant effect on aminopyrine metabolism in hepatocytes in
the presence of standardised methanol extract of Misai Kucing. The possible
mechanism of action ofthe in vitro effect of 1 mg/ml of standardised methanol extract
of Misai Kucing on aminopyrine metabolism in normal old male SD rat hepatocytes
was probably mediated through the activation of G-protein and protein kinase C while
the in vitro effect of 0.001 mg/ml of Misai Kucing extract on normal young female SO
rat hepatocytes was probably mediated through the activation of protein kinase A. The
LOse of standardised of methanol extract of Misai Kucing could not be determined in
this study. No lethality incident and any toxic effects were observed in normal young
male and female SO rats after being treated with 0.5, 1.0, 3.0 and 5 g/kg of
standardised methanol extract of Misai Kucing. Pre-treatment with standardised
methanol extract of Misai Kucing increased the percentage of hepatocytes viability and
decreased some of the serum AST, ALT, ALP and GGT level in 2g/kg of
acetaminophen induced liver damage in adult male and female SO rats. In conclusion,
standardised methanol extract of Misai Kucing had a greater influence on UGT and
GST activity than the aminopyrine N-demethylase activity in SO rat liver. Standardised
methanol extract of Misai Kucing at 0.5 g/kg is classified as not-observable effect level
(NOEL) and it exhibited anti-hepatotoxicity effect on acetaminophen-induced liver
injury in adult male and female SO rats.
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Keywords
Orthosiphon stamineus , Misai Kucing