Effects of Olea europaea L. extract on the rat isolated ileum and trachea

The effects of an Olea europaea L. dried leaf extract containing 3.2% of oleuropein were investigated on the rat isolated ileum and trachea. On basal tone rat isolated ileum, Olea europaea L. extract was shown to produce a dual effect characterized by a contraction at low doses (10^?7-10^?4g/mL) and a relaxation at high doses (3.10^?4-10^?3g/mL). The extract induced contractile effect was found to involve at least histamine, 5-hydroxytryptamine and thromboxane A₂. On precontracted rat isolated ileum, the extract only induced a relaxation that was not modified by nifedipine, diltiazem, dipyridamone, verapamil or papaverine (10^?6 M). The effects of the extract were also studied on the rat isolated trachea. On basal tone organs, Olea europaea L. extract did not produce any effect, whereas, when basal tone was raised by acetylcholine (ACh 10^?3 M), the drug caused a relaxation (maximal effect 39.01% ± 5.40%) of the response to theophylline; (3.10 ± 10^?3M n = 15). It is suggested that the induced relaxation is consecutive to an increase of intracellular 3′5′ cAMP.     

Pharmacological actions of the gut active principles in Croton penduliflorus hutch. Seed on isolated smooth and skeletal muscles and on blood pressure

The effects of Croton penduliflorus seed crystals (CP crystals) were investigated on isolated guinea-pig ileum, chick biventer cervicis muscle and frog rectus abdominis muscle. The effect of the crystals on flood pressure of normotensive Sprague Dawley rats was also investigated. CP crystals induced concentrations-dependent contractions in the guinea-pig ileum with EC₅₀ of 2.39 × 10⁶ g/mL. Contractions induced by CP crystals in the guinea-pig ileum were not inhibited by atropine (2 × 10^?7-1.2 × 10^?6 g/mL), tetrodotoxin (3 × 10^?8-2 × 10^?7 g/mL), hexamethonium (7 × 10^?6-2.8 × 10^?5 g/mL), mepyramine (2 × 10^?7 g/mL) and noradrenaline (2 × 10^?5 g/mL) but were completely (100%) inhibited by indomethacin (7.2 × 10^?6 g/mL). CP crystals (1.0 × 10^?6-5.0 × 10^?4 g/mL) could not elicit contractions in either chick biventer cervicis or frog rectus abdominis muscle. The mean blood pressure of normotensive Sprague Dawley rats was significantly reduced by CP crystals (1.6 × 10^?4-2.5 × 10^?3 g/mL) while the heart rate was significantly reduced by an intravenous infusion of the crystals (2.5 × 10^?3 g/kg) after 2min. The methods employed and the significance of the results obtained are discussed.     

木犀草素对大鼠主动脉的舒张作用及相关机制研究

 目的观察木犀草素的舒血管作用并探讨其作用机制。方法大鼠胸主动脉环张力测定法。结果在内皮完整及去内皮血管上,木犀草素均浓度(4.5～36 μmol·L^-1)依赖性地降低苯肾上腺素(PE)预收缩血管的张力,拮抗高钾引起的血管收缩;木犀草素使PE收缩曲线非平行右移,且使最大张力减小;L-NAME,propranolol对木犀草素的舒血管作用无显著影响;钾通道阻断剂TEA,4-AP,BaCl₂,5-HD均能显著减弱木犀草素的血管舒张作用;木犀草素可以显著地对抗无钙、无钾、无钙环境下渐复钙后由PE引起的血管收缩。结论木犀草素对血管的舒张作用表现为非内皮依赖性,其舒张作用与其直接抑制电压依从性钙通道、受体操纵性钙通道、细胞内钙释放,以及激活钾通道有关,而与α,β受体无关。     

Effects of aqueous extract of Baphia nitida on isolated cardiac tissues

The pharmacological action of cold aqueous extract of fresh leaves of Baphia nitida was studied on cardiac preparations. The extract (5.0 × 10^?3 g mL) reduced the rate and force of contraction of the isolated rabbit heart. The rate and force of contraction of the spontaneously beating rat atria was dose-dependently reduced by 5.0 × 10^?4 to 2.5 × 10^?2 g/mL of the extract and this effect was not antagonized by 3.45 × 10^?7 M atropine. The extract (5.0 × 10^?2 g mL) completely blocked the positive chronotropic and inotropic effects of 10 mM CaCI² but only reduced that of 1.61 × 10^?7 M isoprenaline. The effect of the extract on CaCI₂-induced responses of the rat atria was not affected by 3 × 10^?7 M propranolol. The use of this extract for treating palpitation locally may be related to its negative chronotropic and inotropic effects.     

Hypotensive and spasmolytic activities of ethanolic extract of Capparis cartilaginea

An ethanolic extract of Capparis cartilaginea (CC) at a dose of 1–10 mg/kg caused a dose-dependent fall in blood pressure and heart rate in anaesthetized rats. These effects were not blocked by atropine (1 mg/kg) and pretreatment with CC did not alter the pressor response to norepinephrine, indicating that the cardiovascular effects of CC are independent of cholinergic or adrenergic receptor involvement. In spontaneously beating guinea-pig atria, CC induced a concentration-dependent (0.1–1 mg/mL) decrease in force and rate of atrial contractions. In rabbit thoracic aorta, CC caused inhibition of norepinephrine or K⁺-induced contractions. In guinea-pig ileum, CC (1 mg/mL) inhibited submaximal contractions induced by acetylcholine, histamine or 5-HT. Spontaneous contractions of rat uterus were also abolished when CC was added to the tissue bath at similar concentrations. These results suggest that the direct relaxant action of CC on myocardium and blood vessels may be responsible for its hypotensive and bradycardiac effects observed in the in vivo studies. Moreover, CC exhibits general spasmolytic activity in different smooth muscle preparations.     

Spasmolytic actions of warifteine,a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)

Warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea-pig ileum. The corresponding pD'₂ values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'₂ values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea-pig trachea, the alkaloid inhibited spontaneous tone (IC₅₀, 1.1 × 10^?5M) as well as carbachol induced sustained contractions (IC₅₀, 2.9 × 10^?5M). As warifteine antagonized KCI induced contractions of the guinea-pig ileum (pD'₂ value 4.57±0.10), inhibition of Ca⁺⁺ influx through voltage operated Ca⁺⁺ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca⁺⁺ channels in the ileum.     

The pharmacological basis for the use of dried sheep placenta in traditional obstetric practice in Nigeria

Dried sheep placenta is sometimes used in traditional medicine to facilitate labour. The effects of an extract of powdered dried sheep placenta with normal saline on guinea-pig uterus, ileum, spontaneously beating atrium and Langendorff heart, rat uterus and hindquarters, and cat blood pressure were therefore examined. It was found that 1 g of dried sheep placenta had, on the guinea-pig uterus, an oxytocic activity equipotent with 0.075-0.32 i.u. of oxytocin. The oxytocic activity was unaffected at pHs between 4 and 10 or by boiling for 30 min or autoclaving for 15 min. Neither atropine nor promethazine inhibited the oxytocic action, but promethazine inhibited, to the same degree, contractions induced in the ileum by equipotent doses of the infusion and histamine. Atropine, however, had no effect on infusion-induced contractions in the ileum. The vasoconstriction induced in the rat hindquarters was antagonized by promethazine and phentolamine. Cat blood pressure was reduced, but it had positive inotropic and chronotropic effects on the spontaneously beating guinea-pig atrium and on the guinea-pig Langendorff heart. It was concluded that the dried placenta contains a chorionic oxytocic substance the action of which is independent of stimulation of H₁ receptors or of muscarinic receptors.     

Broncho-vasodilatory activity of fractions and pure constituents isolated from Bacopa monniera

The present study demonstrates that various fractions and sub-fractions isolated from Bacopa monniera produced significant inhibition of carbachol-induced bronchoconstriction, hypotension and bradycardia in anaesthetized rats. All these showed more potency towards inhibition of tracheal pressure compared to either blood pressure or heart rate. The sub-sub fraction and compound 1 caused greater inhibition of tracheal pressure and heart rate compared to blood pressure. Thus, overall bioassay-directed fractionation of B. monniera improved the bronchodilatory activity in various fractions and compound 1 (2-219x) in anaesthetized rats. In vitro, the KCl-induced contraction was equally inhibited by crude extract, petroleum ether and methanol fractions on trachea suggesting bronchodilatory activity remained the same in fractions. On pulmonary artery petroleum ether, dichloromethane and methanol fractions produced 2-2.6 times more vasodilatation compared to crude extract of B. monniera. Subsequent sub-fractions failed to show the existence of broncho-vasodilatory activity, however, the CHCl(3)/MeOH sub-fraction significantly reduced the acetylcholine-induced contraction on ileum. Both the methanol fraction and CHCl(3)/MeOH sub-fraction caused marked reduction of barium chloride-, potassium chloride- and calcium chloride-induced contraction on guinea-pig ileum, indicating their interference with Ca(2+) ion movement. Thus, it may be concluded that various fractions derived from B. monniera possess broncho-vasodilatory activity, which is attributed mainly to inhibition of calcium ions.     

蒙花苷与木犀草素联用对离体血管的舒张作用及其机制研究

为研究蒙花苷与木犀草素联用对SD大鼠离体血管环的舒张作用及其作用机制。采用离体血管环张力实验观察蒙花苷单用(7.5×10~(-6)g·mL~(-1))、木犀草素单用(7.5×10~(-6)g·mL~(-1))、蒙花苷与木犀草素联用(1∶4)对去甲肾上腺素引起的SD大鼠完整、去内皮、L-NAME及吲哚美辛预处理胸主动脉收缩的影响;Western blot检测胸主动脉p-Akt,p-eNOS等蛋白水平。实验结果显示,蒙花苷与木犀草素联用对完整、去内皮及L-NAME预处理的血管环舒张率高于两者单用;且两者联用能显著促进血管中p-Akt,p-eNOS蛋白表达。实验结果说明蒙花苷与木犀草素联用能有效舒张血管,其机制可能是通过激活PI3K/Akt/NO信号通路,增强eNOS活性,从而增加NO的合成与释放,达到舒张血管的作用。     

Pulmonary effects and disposition of luteolin and Artemisia afra extracts in isolated perfused lungs

Ethnopharmacological relevance

Artemisia afra (Asteraceae) is a traditional medicinal plant frequently used in steam inhalation form to treat respiratory conditions.

Aim of the study

Quantify luteolin content in Artemisia afra dried crude and aqueous extract. Evaluate the pulmonary effects of Artemisia afra steam inhalation, nebulized Artemisia afra extract and luteolin in isolated perfused lungs (IPL). Evaluate the pulmonary disposition of intravenously administered luteolin.

Materials and methods

HPLC was used to quantify luteolin in Artemisia afra extracts. A modified version of the IPL was used to determine the effects of Artemisia afra steam inhalation, nebulized luteolin, and nebulized aqueous leaf extract on lung function, as well as the pulmonary disposition of IV luteolin.

Results

Artemisia afra extract contained significantly higher luteolin levels than the crude dried leaves. Inhaled Artemisia afra steam, and nebulized luteolin, and Artemisia afra extract and IV luteolin produced significant dose-dependent improvements in lung function, with nebulized Artemisia afra producing the greatest improvements. Nebulisation with Artemisia afra extract yielded higher quantities of luteolin than luteolin nebulisation.

Conclusion

Results verify the traditional use of inhalation of Artemisia afra steam, although nebulized luteolin and aqueous extract are better alternatives. Luteolin significantly contributes to the bronchodilatory effects of Artemisia afra.     

The Effects of Low and High Concentrations of Luteolin on Cultured Human Endothelial Cells Under Normal and Glucotoxic Conditions: Involvement of Integrin‐Linked Kinase and Cyclooxygenase‐2

Luteolin protects against high glucose (HG)‐induced endothelial dysfunction whereas its cytotoxicity has been reported against normal endothelial cells. This study was undertaken to determine luteolin cytoprotective and cytotoxic dose ranges and to elucidate their respective mechanisms. Luteolin prevented HG‐induced human umbilical vein endothelial cell (HUVEC) death with an EC50 value of 2.0 ± 0.07 μM. The protective effect of luteolin was associated with decreased intracellular reactive oxygen species (ROS) and Ca²⁺ (Cai²⁺) levels and enhanced nitric oxide (NO) production. At high concentrations, luteolin caused HUVEC death in normal glucose (NG) and HG states (LC₅₀ 40 ± 2.23 and 38 ± 1.12 μM, respectively), as represented by increased ROS and Cai²⁺ and decreased NO. Western blots illustrated that exposure to HG increased cyclooxygenase‐2 (COX‐2) and integrin‐linked kinase (ILK) expression. Luteolin at low concentrations suppressed HG‐mediated up‐regulation of COX‐2 but maintained HG‐induced over‐expression of ILK while at high concentrations significantly increased COX‐2 and decreased ILK expression in both HG and NG states. Our data indicated that cytoprotective action of luteolin was manifested with much lower concentrations, by a factor of approximately 20, compared with cytotoxic activity under both normal or glucotoxic conditions. It appears that luteolin exerts its action, in part, by modulating ILK expression which is associated with regulation of COX‐2 expression and NO production in endothelial cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Cardiovascular effects of oblongine chloride,an alkaloid from Leontice leontopetalum,in the anaesthetized guinea-pig

The effects of (?)oblongine chloride, a quaternary alkaloid from Leontice leontopetalum on blood pressure, heart rate and blood flow of the anaesthetized guinea-pig were studied. At doses ranging from 0.5 mg/kg to 30 mg/kg, i.v., oblongine chloride caused a dose-dependent reduction of systolic and diastolic blood pressure. These doses were associated with an increase in heart rate. Propranolol (5 mg/kg) failed to block the effects of oblongine chloride on systolic and diastolic blood pressure but significantly reduced the increase in heart rate observed with low doses (0.5–6 mg/kg) of oblongine chloride. In doses ranging from 0.05 mg/kg to 0.5 mg/kg, oblongine chloride caused a small increase in blood flow. Larger doses (1.5, 4.5, 15 and 30 mg/kg) caused an initial decrease followed by an increase of blood flow. The net effect of cumulative doses was an increase in blood flow over the control value. These observations suggest that oblongine chloride may have potential haemodynamic effects and that these effects are not mediated by β-adrenergic receptor stimulation.     

Coronary vasodilator activity of vulgarenol,a sesquiterpene isolated from Magnolia grandiflora,and its possible mechanism

The aim of this study was to investigate the biodynamic effects of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals and its possible mechanism on the Langendorff isolated and perfused heart model. Vulgarenol (5 µm ) caused a statistically significant decrease in coronary vascular resistance (15.21 ± 6.00 dyn s cm^?5 vs 36.80 ± 5.01 dyn s cm^?5, control group), increased nitric oxide release (223.01 ± 8.76 pmol/mL vs 61.00 ± 12.00 pmol/mL, control group) and cyclic guanosine monophosphate accumulation in left ventricular tissue samples (142.17 ± 8.41 pmol/mg of tissue vs 43.94 ± 5.00 pmol/mg of tissue, control group). Pre‐treatment with 3 µm gadolinium chloride hexahydrate, 100 µm N^ω‐nitro‐l ‐arginine methyl ester hydrochloride, and 10 µm 1H‐[1,2,4]oxadiazolo[4,2‐a]quinoxalin‐1‐one significantly abolished the vulgarenol‐induced coronary vascular resistance decrease, nitric oxide increased release and cGMP accumulation in left ventricular tissue samples. The results support the fact that nitric oxide and cyclic guanosine monophosphate are likely involved in the endothelium‐dependent coronary vasodilation. Copyright © 2008 John Wiley & Sons, Ltd.     

Pharmacological activity of the extracts of two Satureja obovata varieties on isolated smooth muscle preparations

Aqueous extracts of two varieties of Satureja obovata Lag. subsp. obovata: var. valentina and var. obovata, exhibited a dose-dependent inhibitory effect on the contractions induced by acetylcholine (Ach) (3.4 × 10^?8?6.8 × 10^?5M) and CaCl₂ (2 × 10^?4?1.28 ? 10^?2M) in rat duodenum and by noradrenaline (NA) (10^?9?5.12 × 10^?7 M) and CaCl₂ (2 × 10^?4?1.28 × 10^?2 M) in rat aorta. The extracts also produced relaxant effects in both tissue preparations precontracted with K⁺ (75 mM) and in rat aorta precontracted with NA (10^?6 M). Vasodilatory effects of the two extracts were attenuated when the endothelium was removed. The inhibitory effects of var. valentina were stronger. These results indicated a smooth muscle relaxant effect that could account for the use of these extracts in traditional medicine.     

Effect of Citrus paradisi extract and juice on arterial pressure both in vitro and in vivo

Citrus paradisi (grapefruit) consumption is considered as beneficial and it is popularly used for the treatment of a vast array of diseases, including hypertension. In the present study, the coronary vasodilator and hypotensive effects of Citrus paradisi peel extract were assessed in the Langendorff isolated and perfused heart model and in the heart and lung dog preparation. In both models, Citrus paradisi peel extract decreased coronary vascular resistance and mean arterial pressure when compared with control values (60 ± 15 × 10⁷ dyn s cm^?5 vs 100 ± 10 × 10⁷ dyn s cm^?5 and 90 mmHg vs 130 ± 15 mmHg, respectively). These decreases in coronary vascular resistance and mean arterial pressure were blocked when isolated and perfused hearts and mongrel dogs were pre‐treated with L‐NAME. In humans, Citrus paradisi juice decreased diastolic arterial pressure and systolic arterial pressure both in normotensive and hypertensive subjects. Citrus paradisi juice produced a greater decrease in mean arterial pressure when compared with Citrus sinensis juice, cow milk and a vitamin C‐supplemented beverage. However, more detailed studies are required to isolate, purify and evaluate the chemical compounds responsible for this pharmacological effect and to clarify its possible role for treating hypertension. Copyright © 2009 John Wiley & Sons, Ltd.     

The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

远志皂苷H对离体平滑肌与心脏的作用

 目的:研究一种新的远志皂苷H对平滑肌和心肌的药理作用及其机制。方法:制备离体兔回肠,胸主动脉条,Langen-dorf心脏,豚鼠气管条和动情期未孕大鼠子宫标本,记录给药3min后的张力变化。结果:H对上述4种平滑肌均具兴奋作用,19和76μmol·L^-1分别使其张力提高64%和167%,30%和118%,20%和50%,以及100%和180%;对心脏则呈依剂量的抑制作用,19,38和76μmol·L^-1分别使心肌收缩力降低20%,23%和34%,使心率减少17%,20%和35%,但不影响冠脉流量。H对子宫的兴奋作用不受苯海拉明影响,但可被吲哚美辛部分抑制。结论:H对平滑肌具兴奋作用,对心肌具抑制作用,其中对子宫的作用可能部分地与前列腺素合成酶有关。     

Effects of alkaloids from Corydalis decumbens on contraction and electrophysiology of cardiac myocytes

The chloroform extract of Corydalis decumbens significantly increased the beating amplitude of cultured myocardial cell sheets. Chemical analysis led to the isolation of isoquinoline and protopine alkaloids. Of these isolated alkaloids, corlumidine and (+)-adlumidine increased the beating amplitude, but (+)-egenine decreased the beating rate and beating amplitude while protopine did not show any activity. We also studied the effects of (+)-egenine and corlumidine on contractile responses and Ca²⁺ currents in single bullfrog atrial cells using the voltage-clamp method. (+)-Egenine inhibited Ca²⁺ current by 68% of the control in single cell of bullfrog atrium, while corlumidine increased Ca²⁺ current to 60% at a concentration of 0.03 mM.     

Raf and PI3K are the Molecular Targets for the Anti‐metastatic Effect of Luteolin

Metastases are the primary cause of human cancer deaths. Luteolin, a naturally occurring phytochemical, has chemopreventive and/or anticancer properties in several cancer cell lines. However, anti‐metastatic effects of luteolin in vivo and the underlying molecular mechanisms and target(s) remain unknown. Luteolin suppresses matrix metalloproteinase (MMP)‐2 and ‐9 activities and invasion in murine colorectal cancer CT‐26 cells. Western blot and kinase assay data revealed that luteolin inhibited Raf and phosphatidylinositol 3‐kinase (PI3K) activities and subsequently attenuated phosphorylation of MEK and Akt. A pull‐down assay indicated that luteolin non‐competitively bound with ATP to suppress Raf activity and competitively bound with ATP to inhibit PI3K activity. GW5074, a Raf inhibitor, and LY294002, a PI3K inhibitor, inhibited MMP‐2 and ‐9 activities and invasion in CT‐26 cells. An in vivo mouse study showed that oral administration (10 or 50 mg/kg) of luteolin significantly inhibited tumor nodules and tumor volume of lung metastasis induced by intravenous injection of CT‐26 cells. Luteolin also inhibited MMP‐9 expression and activity in CT‐26‐induced mouse lung tissue. These results suggest that luteolin may have considerable potential for development as an anti‐metastatic agent. Copyright © 2012 John Wiley & Sons, Ltd.     

Pharmacological effects of rutin

It is well-known that flavonoids including rutin exert a wide range of pharmacological effects. This study was carried out for further characterization of the pharmacological effect of rutin. A significant rise in the serum 5-HT levels was found 2 h after the administration of rutin (25 mg kg^?1 i.p.). The same dose of rutin caused no significant change in the serum 5-hydroxytryptomine levels after 8 and 72 h when compared to controls. In the in vivo experiments, rutin (25 mg kg^?1 i.p.) was ineffective on the blood pressure and respiratory tract of the guinea-pigs in spite of its smooth muscle relaxant effects in the in vitro preparations. These findings strongly suggest a physiological antagonism in the effects of rutin in intact animals.