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Objective To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum (ZOVR) on live rats and isolated aortic rings of spontaneously hypertensive rats (SHRs). Methods Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract (ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP (HFZOP) with incubation of different antagonists such as Nω-nitro- l -arginine methyl ester (L-NAME, 10 µmol/L), indomethacin (10 µmol/L), methylene blue (10 µmol/L), atropine (1 µmol/L), glibenclamide (10 µmol/L), prazosin (0.01 µmol/L), and propranolol (1 µmol/L). Results During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium. Conclusion This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+ release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.

Introduction Labisia pumila has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects. Objective This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects. Methods Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction. Results WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca2+) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE. Conclusion WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.

Introduction Labisia pumila has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects. Objective This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects. Methods Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction. Results WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca2+) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE. Conclusion WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.

Background: Phaleria macrocarpa (PM) has been used conventionally to cure hypertension. Objective: The objective of the study is to determine the active fraction and its chemical composition responsible for antihypertensive activity of PM fruit using a bioactivity-guided investigation on different extracts of the fruit. Materials and Methods: Among the extracts of PM, water extract (WE) showed prominent effect in screening test by inhibiting noninvasive blood pressure (BP) in spontaneously hypertensive rats (SHRs). WE was investigated further using hypertensive and normotensive experimental models. Results: WE caused dose-dependent hypotensive effect in normotensive rats with adrenergic and cholinergic effects by inhibiting the elevated levels of norepinephrine hydrochloride and acetylcholine hydrochloride induced mean arterial pressure (MAP) and heart rate (HR). In addition, WE enhanced the activity of nonselective β-agonist isoprenaline on MAP and inhibited the increased HR. Similarly, WE demonstrated significant inhibition on pulse wave velocity (PWV), MAP, and HR in SHRs. Fractions of WE were tested for vasorelaxation effect on rat aortic explant. Among the fractions, water fraction-4 (PF-4) showed pronounced effects. Column chromatography of PF-4 yielded two subfractions; among them, sub-fraction-2 (SF-2) displayed significant vasorelaxation effect in endothelium-denuded and endothelium-intact aortas. Further, SF-2 revealed significant inhibition in calcium influx and mobilization from intracellular stores. Gas chromatography-mass spectroscopy analysis of SF-2 revealed abundance of kaempferol 3-O-β glucuronide, mangiferin, gallic acid, and rutin. Conclusions: This study demonstrates that polar phytochemical fraction of PM fruit has a promising potential of reducing PWV, BP, and HR. This antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx. Abbreviations used: WE: Water extract; SHRs: Spontaneously hypertensive rats; NE-HCl: Norepinephrine hydrochloride; MAP: Mean arterial pressure; HR: Heart rate.

Orthosiphon stamineusBenth has been traditionally used to treat hypertension. The study aimed to investigate the vascular reactivity of water extract (WOS) and water : methanolic (1 : 1) extract (WMOS) ofOrthosiphon stamineusBenth and AT1receptors blocker in the mechanisms of antihypertensive mediated byα1-adrenergic receptor and EDNO and PGI2releases in the SHR aortic rings. SHR (230–280 g) were divided into four groups: control, WOS, WMOS, and losartan. After being fed orally for 14 days, the aorta was harvested and subjected to PE (10−9to 10−5 M) and ACh (10−9to 10−5 M) with and without L-NAME (100 µM) and indomethacin (10 µM), respectively. WOS, WMOS, and losartan significantly reduced the contractile responses to PE intact suggesting the importance of endothelium in vasorelaxation. Losartan significantly enhanced the ACh-induced vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively,Orthosiphon stamineusleaves extract reduced vasoconstriction responses by the alteration ofα1-adrenergic and AT1receptors activities. The involvement of EDNO releases was clearly observed in this plant. In WOS, PGI2releases might not participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of vasorelaxation possibly due to continuous release of PGI2.

Objective: This study aimed to investigate the effects of Ficus deltoidea leaves methanolic and water extracts on the vascular reactivity compared with losartan, particularly on the contribution of endothelium-derived relaxing factor, nitric oxide (NO), prostacyclin, and the angiotensin receptor type 1 (AT1) in spontaneously hypertensive rats (SHRs). Method: SHRs (230-280 g) were divided into 4 groups: control (SHRN), losartan (10 mg/kg body weight)(SHRP), Ficus deltoidea methanolic extracts (1 g/kg BW)(SHRM) and Ficus deltoidea water extracts (1 g/kg BW)(SHRW). All groups received daily oral treatment for 14 days. Isolated endothelium intact and denuded thoracic aortic rings were used and subjected to endothelium-dependent and independent contraction studies using phenylephrine (PE) (10-9 to 10-5mol/l). Isolated endothelium intact thoracic aortic rings were harvested and subjected to endothelium-dependent relaxation of acethylcholine (ACh) (10-9 to 10-5mol/l) in the absence and presence of 100 μM Nω-nitro-L-arginine methyl ester (L-NAME) and 10 μM indomethacin. Results: SHRP and SHRW groups reduced significantly vasoconstriction responses to PE in intact aortic rings when compared to denuded. Both SHRN and SHRM groups showed significantly greater tension after removal of endothelium. All groups showed significantly greater relaxation to ACh when compared to SHRN. Inhibition of NO synthesis with L-NAME showed significantly impaired endothelium-dependent relaxation in all groups. However, inhibition of cyclooxygenase (COX) pathway by indomethacin had significantly impaired endothelium-dependent relaxation in SHRP and SHRM groups only. Conclusion: Collectively, these findings suggest that both Ficus deltoidea water and methanolic extracts possess antihypertensive effects but acting on different mechanisms in SHRs. Ficus deltoidea water extract involves endothelium-derived NO but not the prostacyclin pathway, whereas the methanolic extract involves NO/COX pathway. Inhibition of the synergistic activity between AT1 receptor and α1-adrenergic receptor may also possible.