Spasmolytic action of the methanol extract and isojuripidine from Solanum asterophorum Mart. (Solanaceae) leaves in guinea-pig ileum.

Solanum asterophorum Mart. (Solanaceae) is a shrub popularly known as "jurubeba-defogo" in the northeast of Brazil. In the present work, the methanol extract (SA-MeOH, 3750 microg/mL) and isojuripidine (10(-7) - 3 x 10(-4) M), a steroidal alkaloid obtained from S. asterophorum Mart. leaves, inhibited phasic contractions induced by both 1 microM histamine [IC50 = (225.8 +/- 47.4), g/mL and (3.5 +/- 0.8) x 10(-5) M] or 1 microm acetylcholine [IC50 = (112.5 +/- 20.6) microg/mL and (2.3 +/- 0.4) x 10(-5) M] in guinea-pig ileum, respectively. The extract and isojuripidine also relaxed the ileum (SA-MeOH, 1-750 microg/mL, and isojuripidine, 10(-9) - 3 x 10(-4) M) pre-contracted with 1 M histamine [EC50 = (101.1 +/- 17.4) microg/mL and (1.2 +/- 0.3) x 10(-6) M] or 1 microM acetylcholine [EC50 = (136.8 +/- 21.1) microg/mL and (1.9 +/- 0.4) x 10(-6) M] or 40 mm KCl [EC50 = (149.4 +/- 19.5) microg/mL and (1.8 +/- 0.7) x 10(-6) M], respectively, in an equipotent and concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-operated calcium (Ca(v)) channels. To confirm this hypothesis, we evaluated their effect on cumulative CaCl2 curves in depolarizing medium nominally without Ca2+. SA-MeOH (27, 243, 500, and 750 microg/mL) and isojuripidine (3 x 10(-8), 10(-6), 3 x 10(-5), and 3 x 10(-4) M) inhibited the contractions induced by CaCl2, in a concentration-dependent manner. The concentration-response curves to CaCl2, in the presence of SA-MeOH and isojuripidine, were shifted downward in relation to a control curve in a non-parallel manner resulting in reduction of the maximum effect [E(max) = (71.2 +/- 9.2); (57.4 +/- 9.2); (43.8 +/- 3.4); (41.5 +/- 2.4) and (90.6 +/- 4.8); (74.7 +/- 8.7); (66.4 +/- 3.9); (31.3 +/- 4.1)%, respectively]. SA-MeOH and isojuripidine present spasmolytic action in guinea-pig ileum due to a partially blockade of calcium influx through Ca(v) channels.

Morphofunctional alterations of the nonpregnant murine uterus in response to intense and exhaustive exercise are not related to oxidative stress.

Exercise is a common and noninvasive way to improve human health. In contrast, intense exercise causes damage in various tissues and is usually associated with metabolic changes in organs and tissues. Even though intense exercise is associated with dysfunctions in the female reproductive system, much less is known about the cellular mechanisms underlying its effects particularly on the nonpregnant uterus. We investigated whether the effects of an intense and exhaustive exercise (IEE) program on the isolated C57BL/6 uterine morphology and contractility might be related to increased levels of prooxidation markers. Female mice were submitted to 2 days of IEE. The daily exercise session consisted of a running session until exhaustion, with the treadmill speed set at 85% of each animal's maximum velocity. Training responses were evaluated through two parameters: time to exhaustion and maximum velocity. Absence of exercise-induced hypothalamic-pituitary-adrenal (HPA) axis activation was indirectly evaluated by maintenance of the adrenal gland weight. IEE reduced the thickness of the longitudinal muscular layer by 10%, impaired contractility in response to muscarinic stimulation (increased EC50 and decreased Emax), but showed a strong trend to decreasing the KCl-induced contraction; reduced lipid peroxidation; and did not alter the uterine protein oxidation of exercised animals compared with control. Altogether we provide evidence for the nonpregnant murine uterus being an important target to IEE, leading to morphofunctional alterations which could not be associated with tissue oxidative stress but might well be related with exercise-induced uterine dysfunctions.

Antispasmodic activity from Serjania caracasana fractions and their safety

Abstract In a previous study, we reported the antispasmodic and gastroprotective effects of the Serjania caracasana (Jacq.) Willd., Sapindaceae, extract. In the present study, we evaluated the LD50, hemolytic and antispasmodic activities of its fractions and characterized its major constituents by isolation and GC-MS. The animals showed non-toxic symptoms with oral doses up to 2000 mg/kg, suggesting a safe oral administration. Furthermore, a low hemolytic activity was detected for the saponin fraction. Antispasmodic activity of the fractions was evaluated through carbachol-induced contractions in rat ileum. The hexane fraction was the most potent (IC50 68.4 ± 5.9 µg/ml) followed by the dichloromethane fraction (IC50 161.3.4 ± 40.7 µg/ml). Butanol fraction was the less effective (IC50 219.8 ± 60.3 µg/ml). The phytochemical study of the S. caracasana fractions afforded the isolation of friedelin, β-amyrin, allantoin and quercitrin. This is the first time that the presence of allantoin and quercitrin in the Serjania genus has been reported. Among the isolated compounds and those characterized by GC-MS, β-amyrin and β-sitosterol were present in the most active fractions, hexane and dichloromethane, and they may be related to its antispasmodic activity. In addition, spathulenol was only found in the hexane fraction and its presence might justify the highest antispasmodic activity observed for this fraction.

Spasmolytic activity of lapachol and its derivatives, alpha and beta-lapachone, on the guinea-pig ileum involves blockade of voltage-gated calcium channels / Atividade espasmolítica do lapachol e seus derivados, alfa e beta-lapachona, em íleo de cobaia envolve bloqueio dos canais de cálcio dependentes de voltagem

O lapachol, alfa e beta-lapachona são o naftoquinonas obtidas de espécies de Tabebuia, apresentam propriedades antiinflamatória, antibacteriana, anticâncer e tripanossomicida. O objetivo deste trabalho foi investigar um possível efeito espasmolítico destas naftoquinonas em íleo de cobaia, uma vez que, outras naftoquinonas inibem a atividade contrátil de músculos lisos. O lapachol, alfa e beta-lapachona inibiram as contrações fásicas induzidas tanto por carbacol (CI50 = 1,5 ± 0,2 x 10-4; 7,3 ± 0,9 x 10-5 e 3,2 ± 0,5 x 10-5 M, respectivamente) quanto por histamina (CI50 = 3,6± 0,5; 3,6 ± 0,7 e 3,3 ± 0,6 x 10-5 M, respectivamente). Estes compostos também relaxaram o íleo pré-contraído com KCl (CE50 = 1,2 ± 0,4; 4,3 ± 0,8 e 2,7 ± 0,2 x 10-5 M, respectivamente); carbacol (CE50 = 2,6 ± 0,7; 3,5 ± 0,5 e 2,2 ± 0,7 x 10-5 M, respectivamente) ou histamina (CE50 = 3,0 ± 0,8; 1,1 ± 0,3 e 3,3 ± 0,6 x 10-5 M, respectivamente) de maneira dependente de concentração. Este efeito é provavelmente devido à inibição do influxo de Ca2+ através dos canais de Ca2+ dependentes de voltagem (CaV). Beta-lapachona antagonizou (pD'2 = 5,73 ± 0,12; "slope" = 1,51 ± 0,05) as contrações induzidas por CaCl2 em meio despolarizante nominalmente sem Ca2+. O achado de que a beta-lapachona inibiu as contrações tônicas induzidas por S-(-)-Bay K8644 (CE50 = 1,4 ± 0,1 x 10-5 M) é sugestivo que o CaV envolvido é o do tipo L. Em conclusão lapachol, alfa e beta-lapachona apresentam atividade espasmolítica não seletiva em íleo de cobaia, e beta-lapachona exerce este efeito pelo bloqueio dos canais CaV tipo L.

Lapachol, alpha and beta-lapachone are naphthoquinones extracted from species of Tabebuia that have shown antiinflammatory, antibacterial, anticancer and trypanosomicidal properties. The aim of this work was to investigate the spasmolytic effect of these naphthoquinones on the guinea-pig ileum, since other naphthoquinones are known to depress the contractile activity of smooth muscles. Lapachol, alpha and beta-lapachone inhibited the phasic contractions induced by both carbachol (IC50 = 1.5 ± 0.2 x 10-4; 7.3 ± 0.9 x 10-5 and 3.2 ± 0.5 x 10-5 M, respectively) and histamine (IC50 = 3.6± 0.5; 3.6 ± 0.7 and 3.3 ± 0.6 x 10-5 M, respectively). These compounds also relaxed the ileum pre-contracted with KCl (EC50 = 1.2 ± 0.4; 4.3 ± 0.8 and 2.7 ± 0.2 x 10-5 M, respectively); carbachol (EC50 = 2.6 ± 0.7; 3.5 ± 0.5 and 2.2 ± 0.7 x 10-5 M, respectively) or histamine (EC50 = 3.0 ± 0.8; 1.1 ± 0.3 and 3.3 ± 0.6 x 10-5 M, respectively) in a concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-gated calcium channels (Ca v). Beta-lapachone antagonized (pD'2 = 5.73 ± 0.12; slope = 1.51 ± 0.05) CaCl2-induced contractions in depolarizing medium nominally without Ca2+. The finding that Beta-lapachone inhibited the tonic contractions induced by S-(-)-Bay K8644 (EC50 = 1.4 ± 0.1 x 10-5 M) is suggestive that the L-type CaV is involved. In conclusion, lapachol, alpha and beta-lapachone showed non-selective spasmolytic activity in guinea-pig ileum, and beta-lapachone exerts this effect by to blockade of L-type CaV channels.

Avaliação da toxicidade aguda, efeitos citotóxico e espasmolítico de Pomacea lineata (Spix, 1827) (Mollusca, Caenogastropoda) / Evaluation of the acute toxicity, cytotoxic and spasmolytic effects of Pomacea lineata (Spix, 1827) (Mollusca, Caenogastropoda)

Pomacea sp. e sua desova têm uso popular para tratar diarréia e doenças respiratórias. Este trabalho objetivou avaliar a toxicidade aguda e os efeitos citotóxico e espasmolítico dos liófilos de Pomacea lineata e de sua desova. Os liófilos não apresentaram toxicidade aguda (até 2 g/kg v.o.) ou efeito citotóxico (até 1 mg/mL). P. lineata relaxou a traquéia pré-contraída com CCh na presença (Emax = 48,8 ± 6,4 por cento) e na ausência (Emax = 47,3 ± 9,1 por cento) de epitélio, já a desova relaxou apenas na presença (Emax = 36,3 ± 2,5 por cento) de epitélio. Os liófilos foram ineficazes sobre o tônus espontâneo da traquéia. P. lineata foi mais potente em inibir as contrações do íleo induzidas por ACh (logCI50 = 2,5 ± 0,04 µg/mL) que por hist. (logCI50 = 2,7 ± 0,04 µg/mL). A desova inibiu igualmente as contrações induzidas por ACh (logCI50 = 2,5 ± 0,02 µg/mL) e hist. (logCI50 = 2,5 ± 0,06 µg/mL). P. lineata foi mais potente em relaxar o íleo pré-contraído com ACh (logCE50 = 1,7 ± 0,12 µg/mL) do que com KCl (logCE50 = 2,4 ± 0,06 µg/mL) ou hist. (logCE50 = 2,2 ± 0,18 µg/mL). A desova relaxou equipotentemente o íleo pré-contraído com KCl (logCE50 = 2,3 ± 0,15 µg/mL), ACh (logCE50 = 1,9 ± 0,14 µg/mL) ou hist. (logCE50 = 2,2 ± 0,16 µg/mL), sugerindo um bloqueio dos CaV. P. lineata e sua desova apresentam efeito espasmolítico justificando a sua utilização no tratamento de diarréia e de doenças respiratórias.

Pomacea sp. and its eggs are used against diarrhea and respiratory diseases in folk medicine. The aim of this study was to investigate acute toxicity, cytotoxic and spasmolytic activity of lyophilized Pomacea lineata and its eggs. P. lineata and its eggs present no acute toxicity (until 2 g/kg p.o.) or cytotoxic effect (until 1 mg/mL). P. lineata and its eggs have no effect on guinea-pig trachea spontaneous tonus. P. lineata relaxed trachea pre-contracted with CCh in the presence (Emax = 48.8 ± 6,4 percent) and absence (Emax = 47.3 ± 9,1 percent) of epithelium, the eggs relaxed only in the presence (Emax = 36.3 ± 2.5 percent) P. lineata was more potent to inhibit contractions induced by ACh (logIC50 = 2.5 ± 0.04 µg/mL) than histamine (logIC50 = 2.7 ± 0.04 µg/mL). The eggs inhibited contractions induced by ACh (logIC50 = 2.5 ± 0.02 µg/mL) and histamine (logIC50 = 2.5 ± 0.06 µg/mL) in a non-selective manner. P. lineata was more potent in relax ileum pre-contracted with ACh (logEC50 = 1.7 ± 0.12 µg/mL) than KCl (logEC50 = 2.4 ± 0.06 µg/mL) or histamine (logEC50 = 2.2 ± 0.18 µg/mL). The eggs were equipotent in relax ileum pre-contracted with of KCl (logEC50 = 2.3 ± 0.15 µg/mL), ACh (logEC50 = 1.9 ± 0.14 µg/mL) or histamine (logEC50 = 2.2 ± 0.16 µg/mL), that is suggestive of the blockade of the voltage-operated calcium channels. Collectively, the results validate folk use of P. lineata and its eggs to treat diarrhea and respiratory diseases.

Extratos metanólico e acetato de etila de Solanum megalonyx Sendtn. (Solanaceae) apresentam atividade espasmolítica em íleo isolado de cobaia: um estudo comparativo / Methanol and ethyl acetate extracts from Solanum megalonyx Sendtn. (Solanaceae) present spasmolytic activity in guinea-pig ileum: a comparative study

Solanum megalonyx Sendtn. (Solanaceae) é conhecida popularmente por "jurubeba" no Nordeste do Brasil e se apresenta na forma de arbusto. Várias espécies de Solanum apresentam efeito espasmolítico em órgãos isolados. Assim, objetivou-se investigar e comparar o efeito dos extratos metanólico (SM-MeOH) e acetato de etila (SM-AcOEt), obtidos das partes aéreas de S. megalonyx, em íleo isolado de cobaia. SM-MeOH e SM-AcOEt antagonizaram (n = 5) as contrações fásicas induzidas por 1 mM de acetilcolina (logCI50 = 3,2 ± 0,1 e 1,8 ± 0,6 mg/mL, respectivamente) ou de histamina (logCI50 = 2,8 ± 0,5 e 1,7 ± 0,3 mg/mL, respectivamente). SM-MeOH e SM-AcOEt também relaxaram (n = 5) o íleo pré-contraído por 40 mM de KCl (logCE50 = 1,9 ± 0,09 e 1,9 ± 0,1 mg/mL, respectivamente), por 1 mM de histamina (logCE50 = 1,9 ± 0,07 e 1,7 ± 0,08 mg/mL, respectivamente) ou de acetilcolina (logCE50 = 1,9 ± 0,02 e 1,7 ± 0,09 mg/mL, respectivamente) de maneira dependente de concentração e equipotente. Demonstra-se pela primeira vez que S. megalonyx apresenta efeito espasmolítico não seletivo em íleo isolado de cobaia, sugerindo que os extratos podem estar agindo em um passo comum da via de sinalização dos agentes contráteis testados.

Solanum megalonyx Sendtn. (Solanaceae) is known popularly as "jurubeba" in Northeastern Brazil where it can be found as a shrub. Several species of Solanum present spasmolytic effect in several tissues, thus this study was aimed to investigate and compare the effect of the methanol extract (SMMeOH) and ethyl acetate extract (SM-AcOEt), obtained from aerial parts of Solanum megalonyx Sendtn., in guinea-pig ileum. In this work, both SM-MeOH and SM-AcOEt antagonized the phasic contraction induced by acetylcholine 1 mM (logIC50 = 3.2 ± 0.1 and 1.8 ± 0.6 mg/mL) and histamine 1 mM (logIC50 = 2.8 ± 0.5 and 1.7 ± 0.3 mg/mL, respectively) (n = 5), without statistical differences between these values. In another set of experiments, SM-MeOH and SM-AcOEt also relaxed the isolated guinea-pig ileum pre-contracted by KCl 40 mM (logEC50 = 1.9 ± 0.09 and 1.9 ± 0.1 mg/mL, respectively), histamine 1 mM (logEC50 = 1.9 ± 0.07 mg/mL and 1.7 ± 0.08 mg/mL, respectively) or acetylcholine (logEC50 = 1.9 ± 0.02 mg/mL and 1.7 ± 0.09 mg/mL, respectively) (n = 5) in a concentration-dependent and equipotent manner. This study demonstrates for the first time that aerial parts of S. megalonyx present a non-selective spasmolytic effect in guinea-pig ileum, suggesting that the extracts could be acting in a common step of the pathway signaling that leads to contraction induced by the contractile agents tested.