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 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.     

Inhibitory effects of Cistus populifolius on contractile responses in the isolated rat duodenum

The medicinal plant Cistus populifolius L., shows an important dose-dependent spasmolytic activity. The ability of the Cistus extract to inhibit both acetylcholine (ACh) (3.4 × 10⁻⁸–6.8 × 10⁻⁵ M) and CaCl₂ (2 × 10⁻⁴–1.28 × 10⁻² M) -induced contractions and the relaxing effect on K⁺ (75 mM) -induced contractions may indicate a non-specific receptor antagonist. However, this action may be related to the influx of extracellular Ca²⁺. These antispasmodic effects are partly consistent with the use of C. populifolius in folk medicine for certain gastrointestinal disorders.     

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 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.     

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 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.     

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.     

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.     

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.     

醒脑静中各成分对栀子提取物中栀子苷大鼠鼻腔吸收的影响

目的:研究醒脑静中冰片(天然或人工)、人工麝香及合方后对栀子提取物大鼠鼻腔吸收的影响.方法:以体积校正法,采用改良的大鼠在体鼻灌流模型,研究与不同成分配伍后栀子苷的大鼠鼻腔吸收情况.结果:质量浓度为100,250,1 000 mg·L-1的栀子提取物溶液(分别含栀子苷36.8,92,368 mg·L-1)中栀子苷吸收速率常数K分别为(2.15±0.70)×10-3,(1.97±0.48) ×10-3,(1.87±0.81) ×10-3min-1,栀子苷的鼻腔吸收符合一级速率过程,为被动扩散吸收.栀子提取物按组方配比分别与天然冰片(艾片)、人工冰片、人工麝香及合方配伍时栀子苷K值分别为单用栀子提取物组的1.4,1.7,1.1,1.3倍.大鼠鼻腔吸收系数与体外黏膜渗透系数有很好的相关性,KA =0.2206K1+ 0.559(r =0.991 0).结论:醒脑静组方配伍后可显著增加栀子苷的鼻腔吸收,方中冰片发挥了主要的促吸收作用.     

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.     

Herbal medicine Catuama induces endothelium-dependent and -independent vasorelaxant action on isolated vessels from rats,guinea-pigs and rabbits

The present study was designed to examine the vasorelaxant action of the herbal medicine Catuama and the hydroalcoholic extracts (HE) of each plant present in this product and to compare their effects with that caused by acetylcholine (ACh) in intact (⁺E) or in endothelium-rubbed (⁻E) rings of rat thoracic aorta (RA), guinea-pig pulmonary artery (GPPA), guinea-pig mesenteric artery (GPMA), rabbit pulmonary artery (RPA), rabbit mesenteric artery (RMA) precontracted with noradrenaline (NA) or phenylephrine (PE). The extract of Catuama (1-3000 μg/mL) produced graded relaxation of RA, ⁺E or ⁻E, with mean EC₅₀ of 430 μg/mL and ≊ 3000 μg/mL and E_max of 81 % ± 15 % and 47% ± 4 %, respectively. The nitric oxide (NO) synthase inhibitor, N^ω-nitro-L -arginine (L -NOARG, 100 μM ), inhibited in vasorelaxant action (p < 0.05) in RA (⁺E), while indomethacin (3 μM ), propranolol (1 μM ), glibenclamide (1 μM ), methylene blue (10 μM ) and apamin (0.1 μM ) had no significant effect. ACh (1-1000 μM ) caused graded relaxation in RA with ⁺E, these effects being markedly antagonized by L -NOARG (100 μM ), methylene blue (10 μM ) and partially by apamin (0.1 μM ), but not by indomethacin (3 μM ), glibenclamide (1 μM ) or propranolol (1 μM ). The Catuama extract (1-3000 μg/mL) produces partial relaxations in rings of RMA (mean EC₅₀ of 1073 μg7/ml and E_max of 56 % ± 13 %), an effect which was antagonized by L -NOARG (100 μM ). In RPA (⁺E) the extract produces partial relaxation followed by contraction (E_max 28 % ± 6 %), an effect which was abolished by L -NOARG (100 μM ) or methylene blue (10 μM ). The extract caused graded relaxation in rings of GPPA and GPMA with mean EC₅₀ values of 60 μg/mL and 1148 μg/mL and E_max 96% ± 2% and 88% ± 12%, respectively. L -NOARG (100 μM ) blocked the Catuama extract vasorelaxation in GPPA and only partially in GPMA, but markedly antagonized the vasorelaxations caused by ACh in both GPPA andRMA. The HE Paullinea cupana, Zinziber officinalis and Trichilia catigua (1-3000 μg/mL) caused a graded vasorelaxant effect ⁺E of RA with a mean EC₅₀ of 22, 55 and 1793 μg/mL and E_max 100%, 86% ± 7% 70% ± 2%, respectively. In addition the HE of P. cupana also caused graded relaxation in ⁻E of RA with EC₅₀ and E_max of 233 μg/mL and 100%, respectively, while T. catigua and Z. officinalis produced partial relaxation in RA ⁺E. In contrast the HE of Ptychopetalum olacoides caused little contraction (46% ± 14%). These results demonstrate that the medicinal herb Catuama produces significant vasorelaxation responses in vessels from different animal species, and show that its effects are in great part dependent on the release of NO or NO-derived substances. Our results also demonstrate that the vasorelaxant action of the product Catuama seems to be due to the action of the active principles present mainly in P. cupana; T. catigua and, to a lesser extent, in Z. officinalis. Such results may contribute to the explanation of its beneficial effect of Catuama herbal medicine in the management of cardiovascular disturbances. © 1997 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.     

Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice

Morinda citrifolia L. (noni), family Rubiaceae, has been used in Polynesia for over 2000 years for its reputed health benefits, one of which is its therapeutic effects on gout (langa e hokotanga hui). However, its healing mechanism has not been elucidated. This study showed that in an in vitro bioassay that Tahitian Noni^® Juice (TNJ) inhibited xanthine oxidase (XO) concentration dependently. Concentrations of 1, 5 and 10 mg/mL of TNJ inhibited XO by 11%, 113% and 148%, respectively, with an IC₅₀ of 3.8 mg compared with an IC₅₀ of 2.4 µm for allopurinol. Noni fruit juice concentrate (NFJC) also inhibited XO concentration dependently. Concentrations of 1 and 5 mg/mL NFJC inhibited XO in vitro by 184% and 159%, respectively. A 0.1 mg/mL methanol extract (NFJME) from the fractionation of noni fruit puree inhibited XO by 64%. It was elucidated that the noni fruit juice inhibitory effect on XO enzymes is the mechanism by which noni ameliorates gout and gout‐like diseases. Further, the results also support the traditional usage of noni in the treatment of gout. Copyright © 2009 John Wiley & Sons, Ltd.     

莱菔子提取液中萝卜苷的大鼠肠吸收特性考察

目的:考察莱菔子水提液中萝卜苷在大鼠小肠的吸收特性。方法:采用大鼠在体单向肠灌流法考察不同药物质量浓度(0.02,0.05,0.1 g·mL-1)对萝卜苷肠吸收特性的影响,计算吸收速率常数(Ka)和表观吸收系数(Papp)。采用HPLC测定萝卜苷含量,流动相0.1%磷酸溶液-乙腈(87∶13),检测波长225 nm。结果:萝卜苷在pH 5.12的K-R试液中稳定性最好。不同质量浓度的莱菔子水提液中萝卜苷在大鼠小肠的Ka分别为(7.750±1.744)×10-3,(7.204±1.045)×10-3,(7.148±0.837)×10-3min-1,Papp分别为(1.519±0.507)×10-3,(1.504±0.617)×10-3,(1.592±0.345)×10-3cm·min-1,均无显著性变化。结论:萝卜苷为易吸收成分,在大鼠小肠中的吸收机制为被动扩散。     

β-glucuronidase inhibition and diuretic activity of Fabiana imbricata R. & P. (Solanaceae)

The hydroalcoholic extract of Fabiana imbricata inhibited the enzyme β-glucuronidase (β-gluc) in vitro. Bioassay-guided isolation led to scopoletin as the main active constituent of F. imbricata. Scopoletin was a noncompetitive inhibitor of β-D-glucuronidase with a K_i value of 4 × 10^?5 M. A single oral dose of 250 mg/kg body weight F. imbricata extract produced a significant increase (p<0.05) in the urine output of rats. The diuretic effect of the extract was weak in comparison with hydrochlorothiazide at 25 mg/kg. In the acute oral toxicity study in rats, ‘Pichi’ was shown to be a low toxicity crude drug at doses up to 5 g crude extract/kg body weight. At concentrations up to 0.50 mg/mL, the crude extract did not increase the number of chromosome aberrations in the in vitro human lymphocyte assay.     

Endothelium-dependent vasodilator effect of extract prepared from the seeds of Areca catechu on isolated rat aorta

Arecae semen extract relaxed aortic ring preparations of isolated rat aorta that contained endothelium from 3×10⁻⁷ g/mL, reaching a maximum of 86% at 10⁻⁵ g/mL. Its relaxation did not occur in specimens without endothelium, and was inhibited by pretreatment with 10⁻⁴ M N^G-nitro-1-arginine methylester. One of the active components was arecoline which is a muscarinic receptor agonist. Another active component was condensed tannin contained in Arecae semen. © 1997 John Wiley & Sons, Ltd.     

Central inhibitory effects of water extract of Acori graminei rhizoma in mice

The present study evaluated in mice the central inhibitory effects of a water extract of shichangpu (Acori graminei rhizoma (AGR), the dry rhizome of Acorus gramineus Soland. (Araceae)). AGR (0.5–5.0 g/kg) dose-dependently decreased the locomotor activity and increased the pentobarbital-induced sleeping time, but had no significant effect on the treadmill performance. AGR also dose-dependently inhibited the intensity of apomorphine-induced stereotypic behavior. At the highest dose (5.0 g/kg), AGR had a weak anticonvulsant effect on the pentylenetetrazol-induced seizures. Receptor binding assays showed that AGR competed with [³H]SCH-23390 and [³H]YM-09151-2 for specific binding to striatal dopamine D₁ and D₂ receptors with K_i values of 5.6 and 4.2 mg/ml, respectively. AGR also competed with [³H]muscimol for specific binding to the γ-aminobutyric acid (GABA) binding site of cortex GABA_A receptors with a K_i value of 0.31 mg/ml. It also increased the specific binding of [³H]flunitrazepam to the benzodiazepine binding site of the GABA_A receptors, suggesting a GABA agonist-like action. These results suggested that the central inhibitory effects of AGR were probably effected through an action on the central dopamine receptors and GABA_A receptors. The principle of AGR acting at these ligand binding sites was not α-asarone, one of the important principles of AGR, since that α-asarone (10⁻⁶–10⁻⁴ M) had no significant interactions with these binding sites.