Herb - drug interaction: the effect of tinospora crispa miers. on drug metabolism in rat liver
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Date
2009
Authors
Phaik Tin, Tan
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Journal ISSN
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Abstract
Tinospora crispa Miers. (Family: Menispermaceae) or locally known as Patawali or
Akar Seruntum, is a plant that has been used locally as a remedy for diabetes
mellitus, and metabolic disorders. The objective of this study is to investigate the in
vitro and ex vivo effects of the crude extract and different solvent extracts of the
stem of Tinospora crispa on aminopyrine N-demethylase activity in SpragueOawley
(SO) rat liver. n-Hexane, chloroform, n-butanol and aqueous extracts
derived from methanolic-soluble residue of Tinospora crispa were used to
investigate their effects on aminopyrine Phase I metabolism in rat hepatocytes.
Isolated hepatocytes from SO rat liver were prepared using the collagenase
perfusion technique and differential centrifugation technique. The influence of
gender, age and disease (diabetes) were examined on the effects of Tinospora
crispa on aminoyrine N-demethylase activity. Results obtained showed that the
chloroform extract of Tinospora crispa, in vitro, could affect the N-demethylation of
aminopyrine (and probably other drugs that undergo similar Phase I
N-demethylation reaction such as diazepam, morphine and etc). The ex vivo study
of normal and diabetic (STZ-induced) SO rats demonstrated that in young female &
old female (for both normal & diabetic groups) there was a significant effect on
aminopyrine N-demethylase activity. The possible toxic effect of the chloroform
extract of T. crispa in liver and kidney of SO rats was determined. The results in
normal SO rats showed that caution should be exercised for long term intake at
doses 500 mg/kg and more of the chloroform extract of T. crispa because it may
cause toxicity to the liver. However, in diabetic (STZ-induced) SO rats, no
significant change in the clinical biochemistry analysis was observed at 1 0 and 100
mg/kg of chloroform extract of T. crispa. The body weights of the rats were variable
between the groups, depending on different factors, such as gender, age &
disease condition. A total of 6 deaths were reported in several groups which were
administered with 500 mg/kg of the chloroform extract of T. crispa. The in vitro
effect of the chloroform extract of T. crispa on aminopyrine metabolism in young
male diabetic rat hepatocytes was probably mediated through various molecular
pathways i.e. via the cAMP pathway at lower concentrations; as a phosphatase
stimulant and an inhibitor of protein kinase C. In the presence of furafylline, the
chloroform extract of T. crispa enhanced the activity of cytochrome P4501A2ยท In
conclusion, the chloroform extract of T. crispa affected Phase I aminopyrine
N-demethylation in certain groups of rat liver. Caution must be exercised when
using the chloroform extract of T. crispa at doses equal to or greater than 500
mg/kg for the long-term because it significantly elevated the Al T (alanine
aminotransferase) level in adult male rats.
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Keywords
Tinospora crispa miers , Drug metabolism