Vasodilator Effects of the Extract of the Leaves of Cistus populifolius on Rat Thoracic Aorta

The effects of different extracts of Cistus populifolius L. on smooth muscle were studied. The aqueous extract inhibited in a dose dependent manner the noradrenaline (NA) (10⁻⁹–1.03×10⁻⁶ MSC ) and CaCl₂ (2×10⁻⁴–1.28×10⁻² MSC )-induced contractions in rat thoracic aorta. Furthermore, this extract induced relaxant effects in rat aorta precontracted with NA (10⁻⁶ MSC ) and with K⁺ (80 mMSC ). Two different vasodilator responses were observed on NA-induced contractions: one an endothelium-dependent response abolished by methylene blue but not by indomethacin, and the other an endothelium-independent response unaffected by methylene blue and indomethacin similar to that obtained with a flavone, luteolin (10⁻⁵ MSC ). The search for active constituents included a bioactivity-directed fractionation of the lyophilized aqueous extract (LAE) using vascular reactivity experiments. Four different fractions (Cl₂CH₂, Me₂CO, MeOH, H₂O) were analysed at two different concentrations (1 and 2 mg (dry plant)/mL). The methanol fraction was the most active on NA precontracted vascular segments with endothelium, whereas the water fraction was the most active on segments without endothelium. These relaxant effects were less on K⁺ (80 mMSC )-induced contractions. Due to these results we suggest that this plant contains interesting hydrophilic compounds with strong pharmacological action. The endothelium-independent relaxant effect is probably related to flavonoid constituents. However we cannot relate the endothelium-dependent relaxation to known natural compounds in Cistus species. The presence of these constituents with relaxing properties on smooth muscle could account for the use of Cistus plant in traditional medicine.     

Effects of crinum glaucum aqueous extract on intestinal smooth muscle activity

Crinum glaucum aqueous extract (1–8 mg/mL) produced a concentration dependent, non-competitive inhibition of contractions induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and calcium chloride (CaCl₂, 0.05–2 mM ) on the rat duodenum. Contractions of the guinea-pig ileum induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and histamine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) were inhibited by the extract (1–4 mg/mL). The extract (0.125–2.0 mg/mL) also, produced a concentration dependent relaxation of the guinea-pig taenia coli, precontracted with potassium chloride (40 mM ). It is concluded that the extract is a non-specific relaxant of the gastrointestinal smooth muscles used. © 1998 John Wiley & Sons, Ltd.     

Different Effects of Some Isoquinoline Alkaloids from Argemone mexicana on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examines the effects of the extracts [petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Argemone mexicana on the electrically induced contractions of the isolated guinea-pig ileum (E.C.I.). The results of the experiments indicate that CHCl₃/MeOH (9:1) and MeOH extracts, tested at a concentration of 400, 200 and 100 μg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas the petroleum ether and CHCl₃ extracts did not affect it. Furthermore, the partially purified fractions II–V from the MeOH extract, each tested at concentrations of 200, 100 and 50 μg/mL also inhibited E.C.I. Finally the pure compounds 1–2 (5×10⁻⁶–1×10⁻⁵–5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum, whereas compound 3 (5×10⁻⁶–1×10⁻⁵×10⁻⁵ M ) increased them. Since the active compounds 1–3 were respectively identified as protopine, allocryptopine and berberine by NMR, the observed effects could be related mainly to these compounds. © 1997 by John Wiley & Sons, Ltd.     

Pharmacological Actions of Naringin on Alpha,Beta-adrenoceptors and Uptake of Noradrenaline in Rat Isolated Vas Deferens

In normal Krebs solution, naringin (1×10⁻⁷ M sc–2×10⁻⁶ M ) enhanced noradrenaline-induced contractions in rat isolated vas deferens increasing this potentiation in a concentration dependent manner. This enhancing effect continued in the presence of yohimbine (10⁻⁶ M ) or propranolol (10⁻⁶ M ). Naringin did not modify significantly the dopamine dose-response curves. In a medium containing 10⁻⁸ M prazosin, naringin decreased noradrenaline dose-response curves underneath the control curve at all the doses tested. Naringin did not modify significantly the NA dose-response curve in a medium containing cocaine (10⁻⁵ M ) or oestradiol (10⁻⁵ M ). The potentiation produced by naringin on the NA-induced contractions in rat vas deferens may be due to alpha-1 receptor activation, together with an interference of naringin in catecholamine uptake process.     

Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1β- and tumor necrosis factor α-induced adhesion molecule expression in cultured human umbilical vein endothelial cells

We examined the effects of nine flavonoids isolated from Scutellariae radix on interleukin-1β (IL-1β)- and tumor necrosis factor-α (TNF-α)- induced adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVECs). Among them, we found that baicalein (5,6,7-trihydroxy flavone) dose-dependently inhibited IL-1β and TNF-α-induced endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions. Its 50% inhibitory concentrations (IC₅₀) for the IL-1β-induced ELAM-1 and ICAM-1 expressions were 2.3×10⁻⁵ M and 4.0×10⁻⁵ M, respectively. The IC₅₀ for the TNF-α-induced ELAM-1 and ICAM-1 expressions were 1.5×10⁻⁵ M and 3.1×10⁻⁵ M, respectively. In addition, protein C-kinase (PKC) inhibitor H7 also inhibited the ELAM-1 and ICAM-1 expressions induced by IL-1β and TNF-α.     

Inhibiting Activity of Some Glucoindolalkaloids and Iridoids from Sickingia williamsii on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examined the effects of the extracts (petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH), partially purified fractions and pure compounds (mainly alkaloids and iridoids) from Sickingia williamsii on the electrically induced contractions of the isolated guinea-pig ileum. The results of our experiments indicate that CHCl₃/MeOH (9:1) and CHCl₃ extracts, tested at concentrations of 300, 150 and 30 μg/mL, dose-dependently reduced the guinea-pig ileum electrical contractions, whereas MeOH and petroleum ether extracts did not affect it. Furthermore, both the partially purified fractions I–IV each tested at concentrations of 500, 250 and 100 μg/mL from the CHCl₃/MeOH (9:1) extract and some pure compounds (10⁻⁴ M , 5×10⁻⁵ M and 2.5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum. As the active pure compounds possess an indole nucleus or/and an iridoid nucleus in their structures, the inhibitory effects appear to depend on these structures.     

Involvement of calcium in the cardiac depressant actions of a garlic dialysate

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca²⁺]_o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10⁻⁹ to 10⁻⁷ M), verapamil (10⁻⁹ to 10⁻⁷ M) and diltiazem (10⁻⁹ to 10⁻⁷ M) induced a concentration-depe synergism of the log concentration-effect curve of garlic dialysate on left atria. Verapamil and diltiazem (10⁻⁷ M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 × 10⁻¹⁰ to 1.1 × 10⁻⁶ M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca²⁺]_o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.     

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 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.     

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.     

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.     

Pharmacological studies of Striga senegalensis Benth (Scrophulariaceae) as an abortifacient

The methanol extract of Striga senegalensis Benth (Scrophulariaceae) was investigated on isolated rat uterus. Acetylcholine and the methanol extract of the plant produced dose related contractions of smooth muscle of the isolated rat uterus in vitro. Atropine in doses of 2 × 10⁻² to 32 × 10⁻² μg/mL antagonized dose dependently the contraction of the isolated rat uterus produced by both acetylcholine (1.6 × 10⁻¹ μg/mL) and the methanol extract (160 μg/mL). © 1998 John Wiley & Sons, Ltd.     

Xanthine Oxidase Inhibitory Activity of Flavonoids and Tannins from Hexachlamys edulis (Myrtaceae)

The acetone-water extract of Hexachlamys edulis (Myrtaceae) inhibited the enzyme xanthine oxidase (XO) in vitro . Bioassay-guided isolation led to the gallic acid ester in 2″ of myricitrin (desmanthin-1), (-)-epigallocatechin-3-O-gallate (EGG) and pentagalloylglucose as the main XO inhibitors of H. edulis . Desmanthin-1 and EGG were mixed-type inhibitors of XO with K _i values of 1.6×10⁻⁴ M and 1.8×10⁻⁴ M , respectively. Pentagalloylglucose was an uncompetitive XO inhibitor with a K _ESI of 6.7×10⁻⁶M . From the active n -butanol soluble part of the aqueous acetone extract of H. edulis , several flavonoids were isolated. The flavonoids were mainly myricetin-3-O-monoglycosides with the quercetin glycoside avicularin as a minor compound displaying a weak inhibitory activity towards XO.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

Biological Activity and Xanthine Oxidase Inhibitors from Scirpus californicus (C. A. Mey.) Steud.

The methanol extract of the rhizomes of Scirpus californicus (Cyperaceae) inhibited the enzyme xanthine oxidase (XO) in vitro . Bioassay-guided isolation led to piceatannol, scirpusin A and scirpusin B as the main XO inhibitors of S. californicus. Piceatannol, scirpusin A and B were mixed-type inhibitors of the XO with K _i values of 1.1×10⁻⁴, 6×10⁻⁴ and 5×10⁻⁵ M , respectively. The extract and above mentioned compounds were marginally active as hypotensors when tested in normotensive rats at 2.5 mg/kg and were inactive towards the DNA binding assay in vitro.     

Effects of chalcones isolated from licorice roots on leukotriene biosynthesis in human polymorphonuclear neutrophls

The effects of chalcones and flavanones isolated from Sinkiang Licorice (Glycyrrhiza inflata Bat.) on leukotriene B₄(LTB₄) and C₄(LTC₄) formation in human polymorphonuclear neutrophils (PMNs) were investigated. Licochalcone A (2-methoxy-4,4′-dihydroxy-5-α,α-dimethyl-allylchalcone) and licochalcone B (2-methoxy-3,4,4′-trihydroxychalcone), at concentrations of 10^?3 to 10^?6 M, inhibited calcium ionophore A 23187 (A 23187)-induced LTB₄ and LTC₄ formation in human PMNs. The concentration of licochalcones A required for 50% inhibition (LC₅₀) of LTB₄ and LTC₄ formation was 4.6 × 10^?7 and 4.2×10^?6 M, respectively, using 2 μM A 23187. The IC₅₀ values of licochalcone B for LTB₄ and LTC₄ formation were also 1.2 × 10^?6 and 2.0×10^?6 M, respectively. In addition, licochalcones A and B significantly increased cyclic AMP level in human PMNs at concentrations of 10^?4 to 10^?3 M. Licochalcones A and B were found to reduce the elevation of the cytosolic free calcium concentration induced by calcium ionomycine, dose-dependently, in the presence of 1 mM Ca²⁺ or 1 mM EGTA.     

The interactions of paeoniflorin and veratrine on isolated rat atria

In this study, we attemped to identify the interactions and mechanisms between veratrine and paeoniflorin on isolated rat atria. Paeoniflorin alone showed no effect on the rat atria. Veratrine increased the atrial contraction and induced arrhythmia at 1×10⁻⁵ g/ml. Veratrine could directly induce contraction and elicit tetanic contraction at 1×10⁻⁴ g/ml in the left atria with or without electric stimulation. Paeoniflorin (4.8×10⁻⁶ to 4.8×10⁻³ g/ml), verapamil (2.2×10⁻⁶ g/ml), tetrodotoxin (TTX) (3.2×10⁻⁸ g/ml) and quinidine (7.5×10⁻⁶ g/ml) inhibited the increase of contraction and delayed the onset of contraction induced by veratrine (1×10⁻⁵ g/ml). The inhibitory effect of paeoniflorin combined with verapamil on the contraction induced by veratrine was more potent than that of paeoniflorin or verapamil alone. However, the inhibitory effect of paeoniflorin was not potentiated by TTX or quinidine. From the above results, the contraction evoked by veratrine in the rat atria may be concluded to be caused by the stimulation of Na⁺- and Ca²⁺-ion channels. The inhibition of paeoniflorin on the contraction induced by veratrine may primarily be related to the blockade of Ca²⁺ channels.     

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.     

有机硒化合物的抗炎及抗变态反应作用

 目的：有机硒化合物具有多种活性，为此研究3种合成的有机硒化合物的抗炎作用和抗变态反应作用,并分析构效关系。方法：药物对小鼠巴豆油性耳肿胀的影响;对组胺(histamine,His)、过敏性慢反应物质(slow-reacting substance of anaphylaxis SRS-A)所致离体豚鼠回肠收缩的影响;致敏豚鼠肺中SRS-A的提取及药物的拮抗实验。结果：3种化合物能不同程度地抑制小鼠巴豆油性耳肿胀(〖WTBX〗P＜0.05或P〖WTBZ〗＜0.01)。50%抑制离体豚鼠回肠收缩时的药物浓度(IC₅₀)分别为对His:1.25×10^-5,1.58×10^-4，1.25×10^-4 mol/L,对SRS-A:8.9×10^-6，1.25×10^-4，1.12×10^-4mol/L。致敏豚鼠肺释放SRS-A的抑制浓度:10^-4mol/L。结论：3药中9108对受体的拮抗作用最强。该类化合物的化学结构中苯环(B)邻位酯基取代的化合物具有强的受体拮抗作用。它们的抗炎及抗免疫作用与其对His及SRS-A的受体拮抗作用及SRS-A的阻释作用有关。     

Effects of flavonoids from licorice roots (Glycyrrhiza inflata Bat.) On arachidonic acid metabolism and aggregation in human platelets

The effects of six flavonoids isolated from Sinkiang Licorice roots (lichochalcones A and B, isoliquiritigenin, isoliquiritin, liquiritigenin and liquiritin) on arachidonate metabolism and aggregation in human platelets were studied. Licochalcones A and B at concentrations of 10^?5M to 10^?3M inhibited the formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B₂ (TXB₂), does-dependently. Furthermore, isoliquiritigenin and liquiritigenin at higher concentrations (10^?4M–10^?3M) inhibited the formation of HHT and TXB₂, while they increased the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). However, isoliquiritin and liquiritin had no effect on arachidonate metabolism. Licochalcones A and B inhibited thrombin-induced platelet aggregation at concentrations of 2 × 10^?5M to 2 × 10^?4M. Isoliquiritigenin, liquiritigenin, isoliquiritin and liquiritin had no effects on the thrombin-induced aggregation. To clarify the inhibitory effects of flavonoids in licorice roots on the formation of HHT and TXB₂ and thrombin-induced aggregation, we studied the effects of flavonoids on cytosolic free calcium concentrations ([Ca²⁺]i) induced by thrombin. The results showed that licochalcones A and B inhibited the elevation of [Ca²⁺]i induced by thrombin, dose-dependently.