Vascular reactivity, chemical profile, toxicological and pharmacokinetic studies of andrographis paniculata nees. extracts

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Date
2009
Authors
Naidu, Sriramaneni Raghava
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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<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.
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PhD
Keywords
Pharmaceutical science , Vascular reactivity , Toxicological , Pharmacokinetic , Andrographis paniculata nees. extracts
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