Endothelium-dependent contraction of rat thoracic aorta induced by gallic acid

The vascular effect of a component of hydrolysable tannins, gallic acid, was examined in isolated rat thoracic aorta. Gallic acid exerted a contractile effect on the phenylephrine- or prostaglandin F(2/alpha)-precontracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to-gallic acid was absent. Pretreatment with N(G)-nitro-L-arginine methyl ester (30 microM) abolished the gallic acid-induced contraction. Pretreatment with indomethacin (10 microM) or BQ610 (100 nM) had no observed effect. Pretreatment with gallic acid (1-10 microM) significantly attenuated the relaxation induced by acetylcholine, and that with 10 microM gallic acid also reduced the potency of sodium nitroprusside in the relaxation, without a reduction in efficacy, in endothelium-denuded arteries. These findings indicate that gallic acid induced endothelium-dependent contraction and strongly inhibited the endothelium-dependent relaxation rather than the endothelium-independent relaxation, probably through inhibition of endothelial nitric oxide (NO) production. Since NO plays an important role in vasodilative regulation and inflammatory disorders, these findings may also indicate that gallic acid interferes with the inflammatory responses.     

Vasodilator effect of extract prepared from Uncariae ramulus on isolated rat aorta

Uncariae ramulus et Uncus (URE) has a vasodilator effect. Its mechanism consists of not only endothelium-independent relaxation with Ca2+ channel blocking effect but also endothelium-dependent relaxation with nitric oxide. The active components are alkaloids and tannin contained in Uncariae ramulus et Uncus. They also show a superoxide dismutase-like effect and suppressed vasocontraction induced by xanthine and xanthine oxidase. These mechanisms may also influence vasodilatation by Uncariae ramulus et Uncus in vivo.     

Vasorelaxant effect of stilbenes from rhizome extract of rhubarb (Rheum undulatum) on the contractility of rat aorta

The vascular relaxant effect of the rhizome extract of Rheum undulatum was evaluated with isolated rat thoracic aorta preparations. The methanol extract of the rhizome induced a concentration-dependent relaxation of aortic preparations precontracted with 0.3 microm phenylephrine (EC50 value: 5.8 microg/mL). The activity-guided fractionation of the extract led to the isolation of seven hydroxystilbene components as active principles, i.e. piceatannol, resveratrol, desoxyrhapontigenin, rhapontigenin, piceid, rhaponticin and epsilon-viniferin. Of these, piceatannol, a tetrahydroxystilbene, exhibited the most potent vascular relaxant effect in rat aortic preparations (EC50 value 2.4 microm). The vasorelaxant effect of piceatannol on endothelium-intact aorta rings was diminished completely by the removal of functional endothelium or by pretreatment of the aortic tissues with N(G)-nitro-l-arginine methyl ester. These results suggest that piceatannol may be the major mediator responsible for the vasorelaxing properties of the rhizome extract of Rheum undulatum and the vasorelaxant effects of the piceatannol may be mediated via endothelium-dependent nitric oxide signaling pathway.     

Vascular action of the crude hydroalcoholic extract from Hymenaea martiana on the isolated rat and rabbit aorta

The present study investigates the effect of the hydroalcoholic extract (HE) from Hymenaea martiana (Leguminosae) on endothelium-dependent and independent relaxation responses induced by acetylcholine (ACh), histamine (His), calcium ionophore (A23187) and sodium nitroprusside in precontracted aortic rings from rat and rabbit. In addition, we have also evaluated the action of the HE on noradrenaline- (NA), angiotensin I-(AI) and AII-induced contractions in the rabbit aorta. The HE (0.25–0.5 mg/mL) inhibited in a concentration-dependent manner the relaxant response induced by ACh in rings of rabbit aorta and by His in rat aorta. Relaxation in response to A23187 was inhibited in rat but not in rabbit aortic rings. In contrast, the HE was completely ineffective against endothelium-independent relaxations caused/by sodium nitroprusside in rabbit aorta rings. The HE (0.5–1.0 mg/mL) significantly enhanced the maximal contractile responses induced by NA in rabbit aorta set up with the endothelium, but caused no effect in endothelium rubbed preparations. In addition, the HE (0.5 mg/mL) markedly antagonized the contractile responses elicited by AI, but caused only a slight effect on AII-induced contractile responses in rabbit aorta. These findings indicate that the active principle(s) present in the HE from the bark of Hymenaea martiana selectively inhibit the endothelium-dependent vasorelaxant responses caused by several substances in aortic rings from rat and rabbit, presumably by a mechanism related with endothelium-derived relaxation factor synthesis and/or inactivation. The HE also antagonized AI but not AII-induced contractions in rabbit aorta, suggesting some interference with the angiotensin converting enzyme.     

Effects of an aqueous extract of Terminalia arjuna on isolated rat atria and thoracic aorta

Terminalia arjuna (Combretaceae) is used traditionally in ayurveda, to treat a variety of cardiovascular disorders. The aims of this study were to characterize the positive inotropic effect of the aqueous extract of T. arjuna bark in isolated paced rat left atria and to study its effects on a vascular smooth muscle preparation, the rat thoracic aorta. The crude and semipurified aqueous extracts produced a positive inotropic effect of rat atria and the maximum contraction was comparable to that produced by isoprenaline. The positive inotropic effect of the extract was completely blocked by a β-adrenoceptor blocker, propranolol, and an uptake-1 blocker, cocaine. In precontracted aorta, the aqueous extract produced a contraction followed by relaxation. Propranolol did not block the relaxant effect of the aqueous extract. It is concluded that the positive inotropic effect of the aqueous extract was mediated via an action on β₁-adrenoceptors and was likely to be due to the release of noradrenaline from the sympathetic nerve endings. The vasorelaxant effect of the extract, however, was not mediated via an action on β₂ adrenoceptor.     

Arbutus unedo induces endothelium-dependent relaxation of the isolated rat aorta

Arbutus unedo L. (Ericaceae) is used in oriental Morocco to treat arterial hypertension. We studied its vasodilator effect and mechanisms of action in vitro. The root aqueous extract of Arbutus (0.25 mg/mL) produced a relaxation of noradrenaline-precontracted ring preparations of rat aorta with intact endothelium. Relaxation by Arbutus did not occur in specimens without endothelium and was inhibited by pretreatment with 100 microM N(G)-methyl-L-arginine (L-NMA), 10 microM methylene blue or 50 microM 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) but not by 10 microM atropine. These results suggest that Arbutus produces an endothelium-dependent relaxation of the isolated rat aorta which may be mediated mainly by a stimulation of the endothelial nitric oxide synthase by mechanisms other than activation of muscarinic receptors.     

Tannins and catechin gallate mediate the vasorelaxant effect of Arbutus unedo on the rat isolated aorta

This study examined the vascular effect of Arbutus leaves (aqueous extract) and described the isolation of several fractions responsible for their vasorelaxant activity. The aqueous extract (AE) of leaves was tested on rat aortic rings precontracted with 0.1 microm noradrenaline. At 10(-2) g/L, AE produced an endothelium dependent relaxation of 66% +/- 5%, (n = 8). The leaves of Arbutus were then extracted successively with different solvents and the methanol extract was the most active. When tannins (primarily condensed tannins) were precipitated from the methanol extract, they showed a strong vasorelaxant activity (87% +/- 4%, n = 5), whereas the elimination of tannins in the methanol extract reduced significantly its vasorelaxant activity (42% +/- 8%, n = 8, p < 0.005). The methanol extract was further separated semi-preparatively by reversed-phase HPLC. Four fractions (Fr2, Fr3, Fr4 and Fr6) were the most active and produced 88% +/- 2% (n = 5), 75% +/- 6% (n = 5), 76% +/- 3% (n = 7) and 77% +/- 3% (n = 10) relaxation, respectively. These four fractions mainly correspond to polyphenol compounds. Analysis of Fr6 indicated that this fraction contained catechin gallate. In conclusion, the vasorelaxant activity of Arbutus is likely to be due to polyphenol compounds, primarily condensed tannins and catechin gallate.     

Smooth muscle relaxant activities of compounds isolated from malaysian medicinal plants on rat aorta and guinea-pig ileum

Muscle relaxant activities of six compounds isolated from Malaysian medicinal plants were investigated on the smooth muscles of the rat aorta and longitudinal muscle of the guinea-pig ileum. Except for goniothalamin, the other five compounds exhibited varying degrees of muscle relaxant activities on the two smooth muscles. Dicentrine, isocorydine, altholactone and usnic acid reduced the contractions to KCI and phenylephrine in the rat aorta, whilst atranorin slightly reduced the contractions to phenylephrine but not KCI. In addition, dicentrine and isocorydine markedly reduced the contractile response to phenylephrine in Ca²⁺-free Krebs solution. In the longitudinal muscle of the guinea-pig ileum, altholactone, atranorin, dicentrine and isocorydine inhibited to a greater extent the phasic than the tonic responses to KCI. All four compounds similarly inhibited the contractions induced by ACh. The results suggest that the relaxant activities of the compounds are attributed mainly to inhibition of Ca²⁺ influx via the calcium channels in the membrane of the smooth muscles. Furthermore, the greater sensitivity of dicentrine, isocorydine and altholactone against phenylephrine-induced contractions or KCI-induced phasic contractions are due to their abilities to inhibit intracellular Ca²⁺ release in these muscles.     

Terminalia arjuna extract modulates the contraction of rat aorta induced by KCl and norepinephrine

The bark of Terminalia arjuna is in clinical use for the management of cardiovascular disorders in India. The objective of this study was to investigate the contractile response induced by the extract on rat aorta, a vascular smooth muscle. Terminalia arjuna relaxed the contraction, induced by both KCl (60 mM ) and norepinephrine (NE, 3 μM ). Inhibition was more prominent (80%) in the NE induced contraction than the KCl induced contraction (30%). Under similar conditions diltiazem, a calcium channel blocker (Dz, 1.0 μM ), inhibited 68% of the KCl induced and 30% of NE induced contraction. Thus it appears that the action of Terminalia arjuna extract differs from that of diltiazem in that it is more specific for alpha-adrenergic receptor agonists. It indirectly inhibited the contraction induced by norepinephrine by acting on K (Ca) channel by hyperpolarizing the smooth muscle membrane.     

The in vitro effect of aqueous extract of Nigella sativa seeds on nitric oxide production

The in vitro effect of aqueous extract of Nigella sativa seeds on nitric oxide (NO) production by murine macrophages was studied. Murine peritoneal macrophages were pre-incubated with the extract and then activated with Escherichia coli lipopolysaccharride. NO production was measured after 24 hours by spectrophotometry. The plant extract caused a dose-dependent decrease in NO production. Dialyzed preparation of the extract did not affect NO production. However, the boiled fraction of the extract resulted in a dose-dependent inhibition of NO apparently comparable to that of the whole extract. These results indicate that the aqueous extract of N. sativa seeds exhibits an inhibitory effect on nitric oxide production by murine macrophages and the active component(s) is/are non-protein in nature. In view of the fact that nitric oxide is a pro-inflammatory mediator, this study validates the traditional use of the Nigella sativa seeds for the treatment of rheumatism.     

Cardioprotective effect of sasanquasaponin preconditioning via bradykinin‐NO pathway in isolated rat heart

Sasanquasaponin (SQS) is an effective component of Camellia oleifera Abel. This study was designed to investigate the cardioprotective effect of SQS against ischemia‐reperfusion (I/R) injury and the possible mechanism in isolated rat hearts. These hearts were pretreated by SQS only or SQS and HOE140 in different groups, and then subjected to I/R injury. Hemodynamic parameters, oxidative injury, and NO level were measured. The results showed that SQS preconditioning could decrease the incidences of arrhythmias and improve the heart functions. In addition, SQS preconditioning could protect isolated I/R injured heart against lipid peroxidation, as evidenced by increases in SOD and GSH‐Px activity, and by decreases in contents of MDA, ROS generation. However, HOE140 treatment reversed all these indexes. NO production was significantly decreased after a treatment with HOE140. So we can propose that SQS preconditioning could induce the cardioprotective effects and the possible mechanism was that the activation of bradykinin‐NO system by SQS preconditioning had an inhibition effect on ROS generation in isolated heart. Copyright © 2009 John Wiley & Sons, Ltd.     

吴茱萸水提物对乙醇造成的大鼠胃损伤的保护作用

目的：研究吴茱萸水提物对乙醇造成的大鼠急性胃损伤的保护作用及其可能的机制。方法：大鼠经腹腔注射424.8,141.6,47.6 mg·kg^-1 3种不同剂量的吴茱萸水提物后,用ex-vivo chamber法测定50%乙醇造成胃损伤前后的胃电压（PD）变化；另外,经在体胃内插管收集灌流液后,采用硝酸还原酶法测定灌流液中一氧化氮的代谢产物（NO_x）的含量,并通过形态测量法测定胃损伤程度。结果：与对照组比较,不同剂量的吴茱萸水提物对促进PD的恢复和降低损伤指数均有显著作用（P<0.05）,并呈现出剂量依赖性。吴茱萸水提物能剂量依赖性地升高胃损伤前后灌流液中NO_x的水平；尤其当剂量为424.8 mg·kg^-1时,与对照组比较,灌流液NO_x的含量显著增加（P<0.01）。结论：吴茱萸水提物对50%乙醇造成的大鼠急性损伤具有较好的保护作用；其机制与增强胃黏膜屏障功能,促进胃黏膜内源性NO合成有关。     

Antiinflammatory activity of methanol extract isolated from stem bark of Magnolia kobus

The present study reports the antiinflammatory activity of a methanol extract isolated from the stem bark of Magnolia kobus (MK). MK potently inhibited lipopolysaccharide (LPS)-induced production of nitric oxide and interleukin-1beta (IL-1beta) in RAW 264.7 cells, a murine macrophage-like cell line. The secretion of tumor necrosis factor-alpha (TNF-alpha) was also suppressed in LPS-stimulated RAW 264.7 cells although the magnitude of inhibition was weaker than that of nitric oxide and IL-1beta. The mRNA expressions of inducible nitric oxide synthase (iNOS), IL-1beta and TNF-alpha were also suppressed by MK in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced DNA binding of AP-1 and phosphorylation of c-jun N-terminal kinase (JNK) were inhibited by MK treatment in RAW 264.7 cells, whereas phosphorylation of p38 mitogen-activated protein kinase was unaffected. Moreover, topical application of MK suppressed ear swelling in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation model. Collectively, these results suggest that MK exerts antiinflammatory effects in vitro and in vivo and this might be mediated, at least in part, by blocking AP-1 and JNK activation.     

Relaxant effect of ethanol extract of Bacopa monniera on trachea,pulmonary artery and aorta from rabbit and guinea-pig

The relaxant action of an ethanol extract of Bacopa monniera was examined on ring segments of pulmonary arteries (guinea-pig and rabbit), aorta (rabbit) and tracheal preparations (guinea-pig). The plant extract induced relaxation in all the tissues in a dose-dependent manner. Guinea-pig main pulmonary artery was found to be the most responsive to the plant extract, however, complete relaxation was obtained in the tracheal preparations. The relaxant response to the plant extract was unaffected by pretreatment of the blood vessels with either atropine or propranolol, whereas in the tracheal preparations propranolol partially blocked the response. Indomethacin reduced the plant extract-induced relaxation in all the tissues. In blood vessels relaxation induced by the plant extract was not modified in the presence or absence of the endothelial layer. These results suggest that relaxation induced by Bacopa monniera possibly involves prostacyclin compounds (in all the tissues) and β-adrenoceptors (in tracheal preparations). Furthermore, this relaxation is independent of endothelium and muscarinic receptors activation. © 1997 John Wiley & Sons, Ltd.     

Relaxant effects of the neutral extract of the leaves of Bidens pilosa Linn on isolated rat vascular smooth muscle

The long-lasting antihypertensive effect of a neutral extract of Bidens pilosa has been suggested to be due to vasodilation. The present work was undertaken to assess this hypothesis. The vasorelaxant effect of a neutral extract (NBp) of the leaves of B. pilosa was evaluated in vitro on isolated rat aorta contracted with KCl or norepinephrine. NBp induced a concentration-dependent vasorelaxation of the rat aorta precontracted with KCl (60 mM) by 25%-105% at the respective concentrations of 0.25-1.5 mg/mL. The maximal concentration of 1.5 mg/mL provoked 88% relaxation of norepinephrine-induced contractions. There were no significant differences between the effects of the extract on the aorta strips with or without endothelium. In the presence of indomethacin or pyrilamine maleate, the relaxant response induced by the plant extract was significantly inhibited at the lower concentrations. The plant extract was able to reduce the aorta resting tone, inhibit the KCl-induced contractions (90% at 1.5 mg/mL) and the CaCl2-induced contractions by 95% at a concentration of 0.75 mg/mL. These results demonstrate the vasodilating properties of the neutral extract of Bidens pilosa and indicate that it may act as a calcium antagonist.     

藏药1号水提液对大鼠离体胸主动脉条收缩作用的影响

目的：通过观察藏药1号水提液对大鼠离体胸动脉条收缩作用的影响研究其降压机制。方法：观察藏药1号水提液(6mg／mL)和维拉帕米(Ver0.013mg／mL)对高K^ 液引起的主动脉条收缩的时效影响，对KCl，NE及CaCl2引起的大鼠主动脉条收缩的量效曲线的影响，以及对NE引起的依赖于细胞内钙及细胞外钙的收缩的影响。结果：藏药1号水提液抑制高K^ 液引起的主动脉收缩；且可使KCl、NE及CaCl2引起的大鼠主动脉条收缩的量效曲线非平行右移，最大效应降低，呈非竞争性拮抗作用：与维拉帕米相似，对NE引起的依赖于细胞内钙及细胞外钙的收缩均有抑制作用。结论：提示藏药1号的降压机制与钙离子通道拮抗剂一致。     

拳参正丁醇提取液对家兔胸主动脉条收缩的影响

目的:研究拳参正丁醇提取液(PBNA)对家兔离体胸主动脉条的作用。方法:采用家兔离体胸主动脉条,高钾去极化后,以不同浓度CaCl2为刺激剂,观察PBNA对其量-效曲线的影响;以NE为血管收缩刺激剂,观察PBNA对内钙释放与外钙内流的影响。结果:(1)低剂量PBNA(0.1mg/ml)可抑制高钾去极化引起的动脉条收缩,使CaCl2量-效曲线右移,最大反应性降低,高剂量PBNA(0.4mg/ml)可增强高钾去极化引起的动脉条收缩;(2)低剂量的PBNA抑制NE诱导的内钙释放所致的血管收缩反应,而高剂量的PBNA增强NE诱导的内钙释放所致的血管收缩反应;各剂量的PBNA对复钙后NE所致的血管收缩作用具有抑制趋势。结论:不同浓度的PBNA通过抑制或促进平滑肌细胞膜电压依赖Ca2 通道而对家兔主动脉条的收缩起双重效应,PBNA对受体操纵的Ca2 通道也具有一定的抑制作用,对K 通道的开放有一定的促进作用。     

The effect of the aqueous extract of Cynomorium coccineum on the epididymal sperm pattern of the rat

An aqueous extract of Cynomorium coccineum was administered by stomach tube to ten mature male Wistar rats, at a dose of 47 mg/100 kg body weight/day for 14 consecutive days. Ten rats were kept as controls and received normal saline by oral route at the same dosing interval. Sperm was collected from the epididymes after decapitation. The results revealed that the water extract of the Cynomorium coccineum induced significant increase in the sperm count, improved the percentage of live sperm and their motility and decreased the number of abnormal sperm. Testicular histology showed increased spermatogenesis and seminiferous tubules full of sperm in the treated group compared with the controls. Copyright © 1999 John Wiley & Sons, Ltd.     

Differential antagonistic effect of hydroalcoholic extract from Hymenaea martiana hayne arzeik on kinin and other agonist-induced contractions of the isolated rat uterus and Guinea-pig ileum

This study was undertaken to evaluate the action of the hydroalcoholic extract (HE) from the bark of Hymenaea martiana on bradykinin (BK), lysyl-bradykinin (L-BK), acetylcholine (ACh), angiotensin II (AII), prostaglandin F_2a (PGF_2a), serotonin (5-HT), oxytocin (Ot) and histamine (His)-induced contractions of the isolated rat uterine muscle and guinea-pig ileum. The HE (50–200 μg/mL) added to the bath for 20 min caused a concentration-dependent rightward displacement of BK, L-BK and ACh-induced contractions in the rat uterus, allied to a discrete but significant reduction of maximal responses to the latter two agonists. By contrast, at the same range of concentrations the HE antagonized in a concentration-dependent but noncompetitive manner the contractions induced by AII, but only at high concentrations (200 μg/mL) it significantly inhibited contractions evoked by both PGF_2a and Ot, while contractile responses induced by 5-HT were not affected. In the guinea-pig ileum, the HE of H. martiana (50 and 100 μg/ml) caused a discrete rightward displacement of the BK and ACh concentration—response curves. Higher concentrations of the HE of H. martiana (200 μg/mL) caused a marked depression of BK and ACh-induced maximal responses. These findings show that the active principle(s) presents in the HE from the bark of H. martiana exhibits an interesting pharmacological profile against several neurotransmitter-induced contractions in nonvascular smooth muscles. Such actions may be relevant for supporting, at least in part, the use of this plant in folk medicine.     

"脾虚"大鼠胃黏膜组织一氧化氮含量及补中益气汤的作用

目的：研究“脾虚”大鼠胃黏膜组织一氧化氮（NO）含量的变化及补中益气汤的作用。方法：采用Griess试剂法和紫外分光光度法检测胃黏膜组织的一氧化氮代谢产物（NO2^-和NO3^-）和过氧化亚硝酸（ONOO^-）。结果：大黄“脾虚”大鼠胃黏膜组织中NO3^-、iNOS及ONOO^-水平均低于正常大鼠，经补中益气汤治疗后能恢复到接近正常水平。结论：“脾虚”大鼠胃黏膜组织一氧化氮（NO）含量低于正常，补中益气汤能升高“脾虚”大鼠胃黏膜组织中NO的含量。