Vascular reactivity, chemical profile, toxicological and pharmacokinetic studies of andrographis paniculata nees. extracts
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Date
2009
Authors
Raghava Naidu, Sriramaneni
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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<O.OOl) 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 ofthe 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 mglkg in rats.
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Keywords
Chemical profile , PharmacokineticP , Andrographis paniculata