Vascular reactivity, chemical profile, toxicological and pharmacokinetic studies of andrographis paniculata nees. extracts
Loading...
Date
2009
Authors
Naidu, Sriramaneni Raghava
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The aims of the study were to evaluate the vascular reactivity, chemical
profile, toxicity and pharmacokinetic of Andrographis paniculata (AP) extracts.
Andrographis paniculata chloroform extract (APCE) was found to be a potent
vasorelaxant against norepinephrine (NE)-induced contraction of rat thoracic aorta.
The HPLC and 1H-NMR analysis of APCE revealed the presence of andrographolide
(ANG), 14-deoxyandrographolide (DA) and 14-deoxy-11, 12-
didehydroandrographolide (DDA). Chronic treatment for four weeks of APCE 25, 50
and 100 mg/kg/day in spontaneously hypertensive rats (SHR) demonstrated that it
enhances the endothelium-dependent and endothelium-independent relaxation to
acetylcholine (ACh) and sodium nitroprusside (SNP) presumably due to the
activation of nitric oxide (NO) synthase and stimulation of the NO production in
endothelial cells which lead to inhibition of Ca2+-induced contraction pathway. The
systolic blood pressure (SBP) of SHR was significantly (p<0.001) reduced
presumably due to its vasodilatory action on blood vessels.
APCE, sub-fraction of AP (AP1), DA and DDA dose dependently inhibited
both the NE-induced tonic contraction and high K+ (80 mM)-induced contraction,
suggesting that APCE, AP1, DA and DDA act as a Ca2+ channel blocker of both
receptor-operated and potential-dependent channels. DA, DDA and APCE also dose
dependently inhibited the NE-induced phasic contraction, suggesting that DA, DDA
and APCE inhibits the Ca2+ release from sarcoplasmic reticulum. The reduction in
intracellular Ca2+ concentration that contribute to vasorelaxation induced by DA,
DDA and APCE may be through inhibition of Ca2+ influx and inhibitions of
intracellular calcium released. The inhibitory effect of DA, DDA and APCE on
lower dose of NE-induced phasic contraction may act by inhibiting calcium influx
through calcium-independent pathway.
Finally the acute and chronic toxicity studies of APCE at 100, 300, 1000 and
2000 mg/kg/day showed there was no visible sign of toxicity until the end of the 28
days study period. There were no significant changes observed on the weekly body
weight gain and hematological profile as well as macroscopic and histopathological
profile of the internal organs on post mortem. Therefore, the results obtained suggest
that APCE is nontoxic up to 2000 mg/kg body weight. In pharmacokinetic study of
APCE using ANG and DDA as markers showed non-linear pharmacokinetics at a
dose 1000 mg/kg in rats.
Description
PhD
Keywords
Pharmaceutical science , Vascular reactivity , Toxicological , Pharmacokinetic , Andrographis paniculata nees. extracts