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.     

Constituents of Croton menthodorus and their effects on electrically induced contractions of the guinea-pig isolated ileum

The present study examines the effects of the extracts [petroleum ether, CHCl(3), CHCl(3)MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Croton menthodorus on the electrically induced contractions of the isolated guinea-pig ileum (ECI). The results of the experiments indicate that CHCl(3)/MeOH (9:1) and MeOH extracts, tested at concentrations of 100, 50 and 25 microg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas petroleum ether and CHCl(3) extracts did not affect it. Furthermore, the partially purified fractions III-VI from the CHCl(3)/MeOH extract, each tested at concentrations of 100, 50 and 25 microg/mL also inhibited ECI. Finally, pure compound 1 (6 x 10(-6), 3 x 10(-6), 1 x 10(-6) M) isolated and purified from the most active fraction III significantly reduced, in a dose-dependent manner, the electrical contractions of the ileum. Compound 1 was identified by NMR and EI-MS data as the morphinandien-7-one, O-methylflavinantine.     

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.     

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.     

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.     

Flavonol glycosides from Aristeguietia discolor reduce morphine withdrawal in vitro

The effects of extracts, partially purified fractions and four flavonol glycosides 1-4 from Aristeguietia discolor were investigated on the naloxone-precipitated withdrawal contraction of the acute morphine dependent guinea-pig ileum in vitro. After a 4 min in vitro exposure to morphine a strong contraction of guinea-pig isolated ileum was observed after the addition of naloxone. Both MeOH extract (50, 100 and 200 mg/mL), the partially purified fractions I, L, M and N (50, 100 and 200 mg/mL) and flavonol glycosides 1-4 (1 x 10(-4) 5 x 10(-5) 1 x 10(-5) M), injected 10 min before morphine, were capable of blocking the naloxone-induced contraction after exposure to morphine in a concentration-dependent fashion. The results of the present paper suggest that flavonol glycosides from Aristeguietia discolor may play an important role in the control of morphine withdrawal.     

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.     

The pharmacological properties of the ethanolic root extract of Combretum dolichopetalum

The pharmacological actions of the crude ethanolic extract and the active fractions of the roots of Combretum dolichopetalum were tested on guinea-pig isolated ileum and in intact rats. The extract relaxed guinea-pig ileum in a concentration-dependent manner. Two active fractions (R_f 0.96 and 0.84) which also relaxed the guinea-pig ileum were isolated using column chromatography and TLC respectively. Both the crude extract and the active fractions inhibited the contractions induced by acetylcholine and histamine concentration-dependently in the guinea-pig ileum. The crude extract inhibited ulcers and gastric secretions induced in rats by pyloric ligation together with histamine 100 mg/kg, i.p. (p<0.05). The extract also delayed gastric emptying in rats in a dose-dependent manner. The effects of the extract were compared with cimetidine at each stage of the study.     

Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) Extracts Inhibit the Growth of the Breast Cancer Cell Lines MDA‐MB‐231 and MCF‐7, But Not the Brain Tumour Cell Line U251 In Vitro

Zanthoxylum usambarense (Engl.) Kokwaro has traditionally been used for the treatment of malaria, upper respiratory tract infections, cough, rheumatism, tooth decay and sore gums in Kenya and other African countries. Dried ground parts of Z. usambarense were extracted by maceration using methanol (MeOH) at room temperature, extract was dried and reconstituted in 70% aq. MeOH and partitioned against n‐hexane and chloroform (CHCl₃) to obtain MeOH, n‐hexane and CHCl₃ extracts. All extracts were assessed for cytotoxicity against two breast cancer cell lines, MDA‐MB‐231 and MCF‐7, and the brain tumour cell line U251 by the MTT assay. The free‐radical scavenging activity of the extracts was also determined by the 2,2‐diphenyl‐1‐picryhydrazyl (DPPH) assay. In the DPPH assay, the MeOH extract was found to be the most active free‐radical scavenger with a RC₅₀ value of 41.1 × 10^?3 mg/mL. It also displayed significant cytotoxicity against the MCF‐7 cell line (IC₅₀ 42.9 µg/mL) and appeared to have induced cell death through apoptosis. None of the test extracts showed any activity against the U251 cell line at test concentrations. The present findings demonstrated that Z. usambarense could be a potential source for new cytotoxic compounds for possible anticancer drug development. Copyright © 2012 John Wiley & Sons, Ltd.     

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。     

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.     

雷公藤固态生物转化产物化学成分的初步研究

目的:对卫矛科植物雷公藤Tripterygium wilfordii Hook.F的干燥根茎进行固态生物转化后的化学成分进行了初步研究。方法:雷公藤生物转化产物用甲醇提取,依次用石油醚、氯仿、醋酸乙酯、正丁醇萃取,对氯仿部分采用各种柱色谱进行分离纯化,纯化物通过波谱数据分析进行结构鉴定。结果:从具有药理活性的氯仿部分分离到5个化合物,分别鉴定为:Caffeine(1),82-dienabieta-ll,14-dione-19-acid(2),β-Sitosterol(3),Stigmastero1(4),3β-Hydroxy-5α,8α-epidioxyergosta-6,22-diene(5),而雷公藤的主要毒性二萜成分雷公藤甲素和雷公藤内酯却没有被发现。结论:雷公藤的主要毒性二萜成分雷公藤甲素和雷公藤内酯却没有从活性部位氯仿萃取物中分到,证明转化脱毒是有意义的。     

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.     

药用拟层孔菌子实体提取物的抗肿瘤活性研究

目的:测定药用拟层孔菌子实体的石油醚粗提物、乙酸乙酯粗提物和甲醇粗提物的总三萜及总甾醇含量;研究3种粗提物及从乙酸乙酯粗提物中分离得到的三萜类单体化合物的体内抗肿瘤活性。探讨其抗肿瘤活性与总三萜和总甾醇含量的关系。方法:通过分光光度法测定3种粗提物的总三萜和总甾醇含量。通过H22荷瘤小鼠移植模型的体内抗肿瘤实验,观察该真菌子实体的石油醚提取物、乙酸乙酯提取物、甲醇提取物及三萜类单体化合物的抗肿瘤活性进行评价。结果:乙酸乙酯粗提物中总三萜含量和总甾醇含量最高,石油醚次之。从乙酸乙酯层分离得到5个单体化合物:去氢齿孔酮酸,3-酮基-去氢硫色多孔菌酸,去氢齿孔酸,阿里红酸A和阿里红酸C。在体内实验中,乙酸乙酯层抑瘤率效果最佳,当浓度达到1 000mg·kg~(-1)时抑瘤率为64.65%,与阳性药5-氟尿嘧啶(5-Fu)的抑瘤率(59.98%)接近,并且免疫器官指数均有一定的变化。单体化合物2(3-酮基-去氢硫色多孔菌酸)抑瘤率为75.13%,与阳性药物CTX(81.76%)抑瘤率接近,比阳性药5-Fu高。其余4种单体化合物也有一定作用效果。结论:乙酸乙酯提取物及这5种单体化合物能有效抑制肿瘤的生长,并且对机体的免疫力有较好的促进作用,该5种单体化合是药用拟层孔菌子实体的抗肿瘤活性成分,药用拟层孔菌的抗肿瘤活性成分可能是三萜类化合物。     

The spasmolytic activity of extracts and some isolated compounds from the leaves of Morinda morindoides (Baker) Milne-Redh. (Rubiaceae)

Aim

The study was aimed to evaluate the in vitro antispasmodic activity of Morinda morindoides leaves aqueous extract, its soluble fractions and isolated compounds to provide the pharmacological basis for its use for the treatment of constipation and diarrhoea in traditional medicine.

Methods

The antispasmodic activity of each sample was evaluated on acetylcholine (ACh) and the depolarized KCl solution induced contractions on guinea-pig isolated ileum suspended in Tyrode's solution.

Results

At a test concentration of 40 μg/ml in organ bath, the aqueous extract and its petroleum ether soluble fraction showed a spasmogenic effect on both agonists. The diethylether, ethyl acetate, n-butanol and residual aqueous phase soluble fractions from the partition of the aqueous extract exhibited spasmolytic activity producing 47–100% inhibition of contractions induced by both agonists with IC₅₀ values ranged from 6 to 15 μg/ml according to the case. In addition, the n-butanol and residual aqueous phase soluble fractions showed an inhibitory effect of 75 and 66% respectively on low high [K⁺] (25 mM) and 65 and 60% respectively on high [K+] (80 mM). Crude flavonoids showed spasmolytic on both agonists while crude saponins only showed spasmolytic activity on ACh and displayed spasmogenic effect on KCl. Quercetin, quercitrin and rutin exhibited significant antispasmodic effect with IC₅₀ values <0.1 μg/ml. Epoxygaertneroside and gaertneroside showed good antispasmodic activity on both agonists (4 < IC₅₀ < 7 μg/ml).

Conclusion

Morinda morindoides leaves possess spasmogenic and spasmolytic properties that can at least explain and support its traditional use against constipation and diarrhoea respectively.     

Pharmacological activity of a procyanidin isolated from Sclerocarya birrea bark: Antidiarrhoeal activity and effects on isolated guinea-pig ileum

The antidiarrhoeal activity of a procyanidin isolated from the bark of Sclerocarya birrea was studied, using four models of experimentally induced diarrhoea in rats. The cathartic agents used were: magnesium sulphate, castor oil, arachidonic acid and prostaglandin E₂. At doses of 150 mg/kg, the procyanidin showed antidiarrhoeal activity in all the models of experimentally induced diarrhoea. The procyanidin (2.5 μg/mL-0.64 mg/mL) dose-dependently inhibited the phasic contractions of the isolated guinea-pig ileum spontaneous activity; this inhibition was significantly reduced by hexamethonium (10^?4 M ). It also modified the dose-response curves to acetylcholine in a non-competitive way, and relaxed, in a dose-dependent manner, the contractions induced by acetylcholine (10^?7 M ) and KCI (50 mM ), being five times more potent against acetylcholine. The procyanidin modified the biphasic mechanical response evoked by acetylcholine (10^?7 M ) in isolated guinea-pig ileum, inhibiting the phasic response more profoundly than the tonic one. It is concluded that the antidiarrhoeal activity of the procyanidin isolated from S. birrea bark is related to an inhibition in intestinal motility. The way in which it produces this inhibition can be related to an interference with the subsequent events evoked after muscarinic stimulation.     

In Vitro activities of plant extracts from Saudi Arabia against malaria,leishmaniasis, sleeping sickness and Chagas disease

The in vitro activity of the methanol extracts of 51 plants randomly collected from the Kingdom of Saudi Arabia and some of their fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were evaluated against Plasmodium falciparum, Trypanosoma brucei brucei, T. cruzi and Leishmania infantum, as well as toxicity against MRC‐5 fibroblast cells. Ten crude methanolic extracts that demonstrated potent and adequately selective antiprotozoal activity were subjected to solvent fractionation using petroleum ether, ethyl acetate and chloroform. Only three samples showed promising antiprotozoal activity. Argemone ochroleuca (CHCl₃ fraction) showed pronounced activity against P. falciparum_GHA (IC₅₀ 0.32 μg/mL) and T. cruzi (IC₅₀ 0.30 μg/mL) with low cytotoxicity against MRC‐5 cells (CC₅₀ 11.6 μg/mL). Capparis spinosa (EtOAc fraction) showed pronounced activity against P. falciparum_GHA with an IC₅₀ 0.50 μg/mL in the absence of toxicity against MRC‐5 cell line (CC₅₀ > 30 μg/mL). Heliotropium curassavicum (CHCl₃ fraction) showed similar activity against P. falciparum (IC₅₀ 0.65 μg/mL; MRC‐5 CC₅₀ > 30 μg /mL). These three extracts will be subjected for further extensive studies to isolate and identify their active constituents. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of ambrein on smooth muscle responses to various agonists

The pharmacological effects of ambrein (isolated from ambergris) on the contractile responses induced by some agonists in smooth muscle preparations were investigated. Ambrein in the concentration range of 10, 50 and 250 μg/ml decreased the spontaneous contraction of the isolated rabbit jejunum, rat uterus and guinea-pig vas deferens. Ambrein-induced antagonism to acetylcholine (Ach) in the guinea-pig ileum was abolished when the concentration of calcium chloride in the Tyrode's solution was increased to 5 mM/l. Furthermore, ambrein did not antagonise nicotine-induced contractions in the isolated rabbit jejunum or serotonin-induced contractions in the isolated guinea-pig ileum and vas deferens or the rat uterus. However, ambrein in the concentration range of 10, 50 and 250 μg/ml antagonised prostaglandins (PGs) E₂, D₂, F_2α, and oxytocin-induced contractions in the rat uterus in vitro. Ambrein also antagonised (±) noradrenaline and (−) adrenaline-induced contractions in the isolated guinea-pig vas deferens. It is concluded that ambrein-induced non-selective dose-dependent antagonism to the effects of some agonists (Ach, adrenaline, noradrenaline, PGs and oxytocin) in some smooth muscles may be due to the ability of this compound to interfere with the mobilisation of extracellular Ca²⁺ required for muscular contractions induced by these agonists.     

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.     

Inhibitory effects of quercetin on guinea-pig ileum contractions

The inhibitory effect of quercetin on the guinea-pig ileum contractile responses was examined to further clarify its mechanism of action. Quercetin inhibited, from doses of 5 μM , the spontaneous phasic contractions of the guinea-pig ileum, as well as the phasic and tonic components of either acetylcholine- or KCl-elicited contractions, in a dose-dependent way. The former effect was reversible and was unaffected by nicotinic blockade. The tonic component of the contractions was more responsive to quercetin than the phasic component. The inhibition of the tonic contraction was, at least partially, due to the blockade of calcium channels by quercetin, since increasing calcium concentration in the tissue bath reversed the inhibition when the organ was contracted by KCl. Quercetin may also interfere with calcium release from intracellular stores, since it inhibited acetylcholine-elicited phasic contraction even in a calcium-free solution. Finally, quercetin shifted the concentration-response curves to carbachol downwards, without modifying the ED₅₀ of the agonist, whereas the concentration-response curves to CaCl₂ were shifted downwards and to the right. In conclusion, quercetin inhibits the contractile responses of guinea-pig ileum, decreasing the calcium concentration available for contractile machinery.