AIM OF THE STUDY: This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents.
MATERIALS AND METHODS: Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 μM). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and Methylene blue (MB 10 μM), sGC inhibitors; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 μM) a nitric oxide synthase (NOS) inhibitor; atropine (10 μM), a cholinergic receptor blocker; indomethacin (10 μM), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.
RESULTS: SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (Rmax). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation.
CONCLUSION: This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and β-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.
METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques.
RESULTS: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations.
CONCLUSIONS: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress.