RESUMO

Background: Gomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. Aim: To evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedure: The chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. Results: Fifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. Conclusions: This study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

RESUMO

Infusions of Valeriana pilosa are commonly used in Peruvian folk medicine for treating gastrointestinal disorders. This study aimed to investigate the spasmolytic and antispasmodic effects of Valeriana pilosa essential oil (VPEO) on rat ileum. The basal tone of ileal sections decreased in response to accumulative concentrations of VPEO. Moreover, ileal sections precontracted with acetylcholine (ACh), potassium chloride (KCl), or barium chloride (BaCl2) were relaxed in response to VPEO by a mechanism that depended on atropine, hyoscine butylbromide, solifenacin, and verapamil, but not glibenclamide. The results showed that VPEO produced a relaxant effect by inhibiting muscarinic receptors and blocking calcium channels, with no apparent effect on the opening of potassium channels. In addition, molecular docking was employed to evaluate VPEO constituents that could inhibit intestinal contractile activity. The study showed that α-cubebene, ß-patchoulene, ß-bourbonene, ß-caryophyllene, α-guaiene, γ-muurolene, valencene, eremophyllene, and δ-cadinene displayed the highest docking scores on muscarinic acetylcholine receptors and voltage-gated calcium channels, which may antagonize M2 and/or M3 muscarinic acetylcholine receptors and block voltage-gated calcium channels. In summary, VPEO has both spasmolytic and antispasmodic effects. It may block muscarinic receptors and calcium channels, thus providing a scientific basis for its traditional use for gastrointestinal disorders.

RESUMO

The present study examined the chemical composition and antimicrobial and gastrointestinal activity of the essential oils of Elettaria cardamomum (L.) Maton harvested in India (EC-I) and Guatemala (EC-G). Monoterpenes were present in higher concentration in EC-I (83.24%) than in EC-G (73.03%), whereas sesquiterpenes were present in a higher concentration in EC-G (18.35%) than in EC-I (9.27%). Minimum inhibitory concentrations (MICs) of 0.5 and 0.25 mg/mL were demonstrated against Pseudomonas aeruginosa in EC-G and EC-I, respectively, whereas MICs of 1 and 0.5 mg/mL were demonstrated against Escherichia coli in EC-G and EC-I, respectively. The treatment with control had the highest kill-time potential, whereas the treatment with oils had shorter kill-time. EC-I was observed to be more potent in the castor oil-induced diarrhea model than EC-G. At 100 and 200 mg/kg, P.O., EC-I exhibited 40% and 80% protection, respectively, and EC-G exhibited 20% and 60% protection, respectively, in mice, whereas loperamide (10 mg/kg, i.p., positive control) exhibited 100% protection. In the in vitro experiments, EC-I inhibited both carbachol (CCh, 1 µM) and high K+ (80 mM)-induced contractions at significantly lower concentrations than EC-G. Thus, EC-I significantly inhibited P. aeruginosa and E. coli and exhibited more potent antidiarrheal and antispasmodic effects than EC-G.

Assuntos

Elettaria/química , Gastroenteropatias/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Modelos Animais de Doenças , Eucaliptol/química , Eucaliptol/farmacologia , Gastroenteropatias/microbiologia , Bactérias Gram-Negativas/patogenicidade , Guatemala/epidemiologia , Humanos , Índia/epidemiologia , Camundongos , Óleos Voláteis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia

RESUMO

There are several interventions during the first stage of labor that have been studied. Vaginal disinfection with chlorhexidine cannot be recommended. Intrapartum antibiotic prophylaxis is recommended for group B streptococcus-positive women. Antibiotic therapy can be considered in women with term prelabor rupture of membranes whose latency is expected to be >12 hours. Aromatherapy with essential oils through inhalation or back massage can be considered. Immersion in water can be considered. Oral restriction of fluid or solid food is not recommended. In the setting of oral restriction, intravenous fluid containing dextrose at a rate of 250 mL/h is recommended. Upright positions and ambulation are recommended in women without regional anesthesia, and women with regional anesthesia can adopt whatever position they find most comfortable and choose to ambulate or not ambulate. Continuous bladder catheterization cannot be recommended. There is no recommended frequency of cervical examinations or sweeping of membranes. The use of a partogram cannot be recommended as a routine intervention. Routine use of the peanut ball cannot be recommended. Antispasmodic agents cannot be recommended. Routine amniotomy alone in normally progressing spontaneous first stage of labor cannot be recommended. Oxytocin augmentation is recommended to shorten the time to delivery for women making slow progress in spontaneous labor, and higher doses of oxytocin can be considered. Early intervention with oxytocin and amniotomy for the prevention and treatment of dysfunctional or slow labor is recommended. Routine use of intrauterine pressure catheter and ultrasound cannot be recommended. Cesarean delivery for arrest should not be performed unless labor has arrested for a minimum of 4 hours with adequate uterine activity or 6 hours with inadequate uterine activity in a woman with rupture of membranes, adequate oxytocin, and ≥6 cm cervical dilation.

Assuntos

Trabalho de Parto Induzido , Trabalho de Parto , Cesárea , Feminino , Humanos , Primeira Fase do Trabalho de Parto , Ocitocina , Gravidez

RESUMO

Croton zehntneri is a plant well adapted to the semi-arid climate of northeastern region of Brazil. The essential oil of C. zehntneri (EOCz) has been described to have several pharmacologic properties, including effect on airflow resistance of in vivo respiratory system. For this reason, we investigated the hypothesis that EOCz and its major constituents, anethole and estragole, have antispasmodic activity on tracheal muscle. In tracheal rings of Wistar rats, maintained in Krebs-Henseleit's solution, EOCz, anethole and estragole inhibited contractions induced by 60mM [K+], ACh (10µM), Ba2+ and Phorbol dibutirate (1 µM). For EOCz, anethole and estragole, the IC50 for inhibition of KCl-induced contractions were 145.8 ± 14.8, 89.9 ± 7.4 and 181.0 ± 23.3 µg/mL, respectively, and for ACh-induced contraction, they were 606.1 ± 122.0, 160.5 ± 33.0 and 358.6 ± 49.2 µg/mL. Pharmacodynamic efficacy was maximal in all cases. These data in Ba2+-induced contraction and the differential IC50 suggested that blockade of Voltage Dependent Calcium Channels (VDCC) is a component of the mechanism of action of the three agents. Evaluation of the direct effect of anethole, on VDCC, showed inhibition of the Ca2+ current through this type of channel. These results show that EOCz and the constituents have antispasmodic activity and the mechanism includes blockade of VDCC channels.

RESUMO

Resumen El síndrome de intestino irritable se caracteriza por la existencia de dolor abdominal relacionado con cambios en el ritmo evacuatorio. A pesar de los avances en el conocimiento de su fisiopatología y de la aparición de nuevas formas terapéuticas, los antiespasmódicos se han mantenido en el tiempo como una forma efectiva para el manejo de los síntomas de este síndrome, en especial para el dolor. Así pues, el propósito de esta revisión es la búsqueda de evidencia científica que soporte el uso de antiespasmódicos en el manejo de los síntomas del síndrome de intestino irritable.

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Abstract Irritable bowel syndrome is a disorder characterized by abdominal pain related to changes in bowel movements. Despite the progress made in the knowledge of its pathophysiology and the emergence of new therapeutic forms, antispasmodics have remained over time as an effective way to treat symptoms, especially pain. The purpose of this review is to search for scientific evidence on the use of antispasmodics in the treatment of irritable bowel symptoms.

Assuntos

Humanos , Síndrome do Intestino Irritável , Dor , Dor Abdominal

RESUMO

Resumen El uso de los antiespasmódicos forma parte de la piedra angular del tratamiento en el síndrome de intestino irritable (SII), independientemente del subtipo. Consideramos relevante hacer una revisión de los medicamentos antiespasmódicos disponibles actualmente en Colombia, los cuales son usados crónicamente, de manera frecuente, en esta enfermedad.

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Abstract Although antispasmodics are the cornerstone of treating irritable bowel syndrome, there are a number of antispasmodic medications currently available in Colombia. Since they are frequently used to treat this disease, we consider an evaluation of them to be important.

Assuntos

Humanos , Papel (figurativo) , Terapêutica , Preparações Farmacêuticas , Síndrome do Intestino Irritável , Parassimpatolíticos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In the Leticia-Amazonas area, Uitoto indigenous people use a preparation of Curarea toxicofera (Wedd) Barneby & Krukoff (Menispermaceae) alone or combined with prescribed medications to prevent and treat malaria. AIM OF STUDY: To determine the in vitro and in vivo antiplasmodial activity of traditional preparations of Curarea toxicofera alone and in combination with classical antimalarials. MATERIAL AND METHODS: The traditional preparation was evaluated in vitro against P. falciparum FCR3 CQ resistant strain, alone and combined. The preparation was further administered orally alone or combined with chloroquine and artesunate in mice infected with Plasmodium berghei ANKA strain on the four-day antimalarial test model. RESULTS: The herbal remedy used alone was able to significantly decrease the parasitemia both in vitro (IC50 7.3 µg/ml) and in vivo (ED50 328 mg/Kg) but it was less active than chloroquine (IC50 0.29 µg/ml in vitro and ED50 2.3 mg/Kg/day in vivo), and than artesunate (IC50 0.002 µg/ml and ED50 3.7 mg/Kg/day). Interestingly it presented synergism with chloroquine in vitro (Combination Index: 0.39) and in vivo; and was additive with artesunate in vitro (Combination Index: 0.94) and in vivo. CONCLUSION: The traditional preparation showed potential as an antimalarial and, when used in combination, does not negatively affect the efficacy of the drugs evaluated. Pre-clinical studies should be conducted with a standardized preparation to confirm its efficacy and safety alone and in combination with chloroquine and artesunate.

Assuntos

Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Malária/tratamento farmacológico , Menispermaceae , Parasitemia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Antimaláricos/farmacologia , Artemisininas/farmacologia , Artesunato , Cloroquina/farmacologia , Quimioterapia Combinada , Malária/parasitologia , Camundongos , Fitoterapia , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos

RESUMO

Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague-Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX2, IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na+K+ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl2. This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.

Assuntos

Colite/induzido quimicamente , Colite/tratamento farmacológico , Ácido Gálico/análogos & derivados , Extratos Vegetais/uso terapêutico , Ácido Acético/toxicidade , Animais , Colite/patologia , Relação Dose-Resposta a Droga , Feminino , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Camundongos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. AIM OF THE STUDY: To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. METHODS: The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca2+) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. RESULTS: Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca2+-CRC, with IC50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a maximal relaxation that was 1.9 times higher than that of papaverine. In the isolated heart, EO-Bs induced a poor negative inotropic response, and did not improve the contractile and energetic recovery after ischemia and reperfusion. In the mouse cough model, EO-Bs (90mg/Kg) was as effective as codeine (30mg/Kg) in reducing cough frequency. CONCLUSIONS: The results indicate that the preparations from Blepharocalyx salicifolius leaves were effective as central antitussive, bronchodilating and antispasmodic agents, suggestive of a mechanism associated with the inhibition of Ca2+ influx into smooth muscle. The EO-Bs displayed only a poor ability to reduce cardiac inotropism, and was devoid of any cardioprotective properties. Thus, the present study validates the traditional use of this South American plant for asthma, cough and bronchospasm, shedding new light into its potency and putative mechanism of action.

Assuntos

Medicina Tradicional/métodos , Myrtaceae/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Antitussígenos/administração & dosagem , Antitussígenos/isolamento & purificação , Antitussígenos/farmacologia , Broncodilatadores/administração & dosagem , Broncodilatadores/isolamento & purificação , Broncodilatadores/farmacologia , Cálcio/metabolismo , Cardiotônicos/administração & dosagem , Cardiotônicos/isolamento & purificação , Cardiotônicos/farmacologia , Tosse/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Masculino , Camundongos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/isolamento & purificação , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/isolamento & purificação , Parassimpatolíticos/farmacologia , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos Sprague-Dawley , América do Sul

RESUMO

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.

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora caerulea L. (Passifloraceae) is a medicinal plant commonly used in traditional medicine in South America for different pathologies associated with the gastrointestinal tract. AIM OF THE STUDY: In the present study, the activity of the ethanolic extract of P. caerulea on an experimental colitis model related to inflammatory bowel disease has been investigated. MATERIALS AND METHODS: Colitis was induced by intracolonic instillation of a 2mL of 4% (v/v) acetic acid solution. Macroscopic scoring, myeloperoxidase activity and thiobarbituric acid reactive substances levels were evaluated on isolated colon mucosae. The histopathological studies of colon mucosae were performed by hematoxylin and eosin and Alcian blue staining. Diarrhoea was induced by the administration of castor oil (0.3mL/mouse). The first watery defecation time, the total amount of solid, semi-solid and watery stools and the amount of watery stools were determined. The effect of the extract on a cumulative concentration-response curve of acetylcholine and CaCl2 on isolated rat jejunum was also evaluated. The phytochemical analysis was performed. RESULTS: The extract (250mg/kg, p.o.) induced a significant reduction in the weight/length ratio, the macroscopic lesion score, TBARS levels and the microscopic tissue damage when compared with the acetic acid-treated group of animals. P. caerulea (125mg/kg, p.o.) decreased significantly the amount of watery stools in the castor oil-induced-diarrhoea model. Moreover, the P. caerulea extract antagonized the jejunum contractions induced by Ach (Emax for 0.3mg/mL: 76.25%; Emax for 1mg/mL: 63.47%; Emax for 3mg/mL: 42.01%) and CaCl2 (Emax for 0.3mg/mL: 75.69%; Emax for1 mg/mL: 56.1%; Emax for 3mg/mL: 53.4%). Isoorientin, vitexin, isovitexin, and vicenin-2 were identified in the extract. CONCLUSION: P. caerulea showed anti-inflammatory, anti-diarrhoeal and spasmolityc activities on preclinical models.

Assuntos

Colite/tratamento farmacológico , Modelos Animais de Doenças , Passiflora/química , Extratos Vegetais/uso terapêutico , Animais , Feminino , Camundongos

RESUMO

The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1-100 µg·mL(-1)) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 µM, potassium chloride (KCl) 60 mM or Bay K8644 1 µM were reduced by EOCM (30 µg·mL(-1)). Apamin 1 µM and charybdotoxin 0.01 µM decreased the inhibition induced by EOCM. The d-cAMP 1 µM decreased the inhibition induced by EOCM. l-NNA 10 µM, Rp-8-Br-PET-cGMPS 1 µM, d,l-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca(2+), Ca(2+)-activated K⁺ channels and cAMP.

Assuntos

Íleo/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Óleos Voláteis/administração & dosagem , Parassimpatolíticos/administração & dosagem , Óleos de Plantas/administração & dosagem , Animais , Apamina/administração & dosagem , Asteraceae/química , Cálcio/metabolismo , Humanos , Íleo/patologia , Músculo Liso/efeitos dos fármacos , Óleos Voláteis/química , Parassimpatolíticos/química , Óleos de Plantas/química , Cloreto de Potássio/química , Coelhos

RESUMO

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 µg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 µg/mL) inhibited carbachol or histamine-induced phasic contractions (1 µM) in a significant and concentration-dependent manner. In addition, XL-OE (81 µg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.

Assuntos

Óleos Voláteis/química , Parassimpatolíticos/química , Óleos de Plantas/química , Xylopia/química , Animais , Aorta/efeitos dos fármacos , Cálcio/química , Citosol/química , Diterpenos/química , Feminino , Cobaias , Íleo/efeitos dos fármacos , Células Musculares/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Folhas de Planta/química , Ratos , Traqueia/efeitos dos fármacos , Útero/efeitos dos fármacos

RESUMO

A síndrome do intestino irritável (SII) é um distúrbio funcional do trato digestivo altamente prevalente, que causa significativo prejuízo da qualidade de vida e impacto econômico e no sistema de saúde. A fisiopatologia da SII é complexa e envolve alterações da motilidade intestinal, bem como aumento da sensibilidade visceral. Pela inexistência de um tratamento etiológico da SII, a abordagem terapêutica usual visa promover o alívio dos sintomas e a melhora da qualidade de vida. Juntamente com a dieta rica em fibras os antiespasmódicos são as medicações mais utilizadas no tratamento da SII. Assim, discutimos a eficácia e a segurança das medicações antiespasmódicas no tratamento da SII.

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: An ethnopharmacological survey indicated that the bark from Qualea parviflora Mart. (Vochysiaceae) could be used to treat gastrointestinal disorders, such as diarrhea and intestinal inflammation. The objective of this study was to evaluate the effects of a methanolic extract from the bark of Qualea parviflora (QP) in an experimental model of diarrhea and intestinal inflammation induced in rodents. MATERIAL AND METHODS: The antidiarrheal and antispasmodic effects of QP were investigated by measuring intestinal motility, diarrhea, and intestinal fluid accumulation in rodents after challenging with a cathartic agent. In addition, the effects of QP on the contractility of the isolated mice-ileum preparation were determined. Acute intestinal inflammation was induced in male Wistar rats by the rectal administration of trinitrobenzenesulfonic acid (TNBS) in 50% ethanol (0.25 mL). QP was administered orally (for 5 days) prior to the induction of inflammation. The colonic injury and extent of inflammation were assessed by macroscopic damage scores and lesion length. The enhanced colonic mucosal injury, inflammatory response, and oxidative stress were evaluated by myeloperoxidase (MPO) activity; the tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL1-ß), and malondialdehyde (MDA) levels; and the glutathione (GSH) content. RESULTS: Oral treatment with QP (500 mg/kg) delayed the onset of diarrhea, reduced the amount of liquid stool, and decreased the severity of the diarrhea and the evacuation index in rodents challenged with castor oil (p<0.01). Additionally, QP (150-500 µg/mL) demonstrated effective antispasmodic activity against carbachol-induced contractions of mouse ileum in vitro. Oral treatment (25 and 50 mg/kg/day) with QP significantly reduced the intestinal inflammation induced by TNBS in rats (52% and 45%, respectively). Improvement of colonic mucosal injury by treatment with QP was demonstrated by a decrease in MDA levels and an increase in GSH content in colonic tissue. QP also prevented intestinal inflammation as evidenced by reduced cytokine levels (TNF-α and IL1-ß) and low MPO activity. CONCLUSIONS: The ethnopharmacological usefulness of the bark from Qualea parviflora against diarrhea containing blood and mucus was supported by the observed antidiarrheal, antispasmodic, and intestinal antiinflammatory properties of this medicinal plant.

Assuntos

Anti-Inflamatórios/uso terapêutico , Antidiarreicos/uso terapêutico , Colite/tratamento farmacológico , Diarreia/tratamento farmacológico , Parassimpatolíticos/uso terapêutico , Extratos Vegetais/uso terapêutico , Traqueófitas , Animais , Anti-Inflamatórios/farmacologia , Antidiarreicos/farmacologia , Óleo de Rícino , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Glutationa/metabolismo , Íleo/efeitos dos fármacos , Íleo/fisiologia , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Metanol/química , Camundongos , Contração Muscular/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Peroxidase/metabolismo , Fitoterapia , Casca de Planta , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Solventes/química , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent-pimaradienoic acid (1, PA, ent-pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30°C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent-pimara-8(14),15-dien-19-oic acid (2), and three new derivatives, 1ß-hydroxy ent-pimara-6,8(14),15-trien-19-oic acid (3), 1α,6ß,14ß-trihydroxy ent-pimara-7,15-dien-19-oic acid (4), and 1α,6ß,7α,11α-tetrahydroxy ent-pimara-8(14),15-dien-19-oic acid (5), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation (2-5) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent-pimara-8(14),15-dien-19-oate (8), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure-activity relationship investigations.

Assuntos

Aspergillus niger/metabolismo , Diterpenos/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Asteraceae/metabolismo , Biotransformação , Diterpenos/química , Diterpenos/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Conformação Molecular , Contração Muscular/efeitos dos fármacos , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Estereoisomerismo , Relação Estrutura-Atividade

RESUMO

ETHOPHARMACOLOGY RELEVANCE: Lippia alba (Mill.) N. E. Brown (Verbenaceae) is an aromatic species used in Central and South America as eupeptic for indigestion. In Argentina, it is used by the "criollos" from the Chaco province. There are several chemotypes which differ in the chemical composition of the essential oils. Nowadays, it is experimentally cultivated in some countries of the region, including Argentina. AIM OF THE STUDY: To compare the chemical composition and pharmacology of the essential oils from two chemotypes: "citral" (CEO) and "linalool" (LEO), in isolated rat duodenum and ileum. METHODS: Contractile concentration-response curves (CRC) of acetylcholine (ACh) and calcium in 40mM K(+)-medium (Ca(2+)-CRC) were done in isolated intestine portions, in the absence and presence of CEO or LEO at different concentrations. RESULTS: Likewise verapamil, CEO and LEO induced a non-competitive inhibition of the ACh-CRC, with IC50 of 7.0±0.3mg CEO/mL and 37.2±4.2mg LEO/mL. l-NAME, a NO-synthase blocker, increased the IC50 of CEO to 26.1±8.7mg CEO/mL. Likewise verapamil, CEO and LEO non-competitively inhibited the Ca(2+)-CRC, with IC50 of 6.3±1.7mg CEO/mL, 7.0±2.5mg LEO/mL and 0.24±0.04mg verapamil/mL (pIC50: 6.28). CEO was proved to possess limonene, neral, geranial and (-)-carvone as the major components, while LEO was rich in linalool. CONCLUSIONS: Results suggest that CEO has five times more potency than LEO to inhibit muscarinic contractions. The essential oils of both chemotypes interfered with the Ca(2+)-influx, but with an IC50 about 28 times higher than that of verapamil. Moreover, CEO partially stimulated the NO production. These results show the medicinal usefulness of both Lippia alba chemotypes, thus validating its traditional use, potency and mechanism of action.

Assuntos

Lippia/química , Óleos Voláteis , Parassimpatolíticos , Óleos de Plantas , Animais , Argentina , Relação Dose-Resposta a Droga , Duodeno/efeitos dos fármacos , Feminino , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Medicina Tradicional , Contração Muscular/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Parassimpatolíticos/química , Parassimpatolíticos/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Ratos , Ratos Sprague-Dawley , Espasmo/tratamento farmacológico

RESUMO

Introducción: Cassia uniflora Mill se emplea en el control aleloquímico de Parthenium hysterophorus; se ha reportado que presenta actividad larvicida frente a Aedes aegypti. Tradicionalmente se ha usado como antiespasmódico y para el tratamiento de erupciones cutáneas. Objetivo: realizar un tamizaje fitoquímico a los extractos etéreo, alcohólico y acuoso de la especie Cassia uniflora Mill para conocer los metabolitos secundarios que sean de interés biológico en la terapéutica. Métodos: se recolectaron partes aéreas y subterráneas de la planta, se lavaron, desinfectaron, secaron, pulverizaron y se sometieron a extracciones sucesivas con solventes de polaridad creciente. Los extractos se filtraron y se realizaron ensayos fitoquímicos de identificación. Resultados: el tamizaje fitoquímico, efectuado a los extractos etéreo, alcohólico y acuoso de las hojas, tallos, cáscaras de los frutos, semillas y raíces, demostró la existencia de varias familias de metabolitos secundarios de interés biológico y farmacológico, entre los que se destacan, por su significativa presencia, las quinonas y las coumarinas. Conclusiones: de acuerdo con la diversidad de metabolitos secundarios presentes en las partes evaluadas de C. uniflora, así como los efectos biológicos reportados para la especie, sería interesante realizar nuevos estudios que aporten evidencias sobre su eficacia y seguridad, como forma de avalar su empleo tradicional.

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Introduction: Cassia uniflora Mill is used for the allelochemical control of Parthenium hysterophorus; and its larvicidal activity on Aedes aegypti has been reported. It has also been applied as antispasmodic agent and as treatment of cutaneous rash. Objective: to perform a phytochemical screening on alcoholic, ethereal and aqueous extracts from the Cassia uniflora Mill species to identify the secondary metabolites of biological interest in therapeutics. Methods: aerial and underground parts of the plant were harvested, washed, disinfected, dried, powdered and subjected to successive extractions with solvents of increasing polarity. The extracts were filtered to carry out phytochemical tests for identification. Results: the phytochemical screening of ethereal, alcoholic and aqueous extracts from leaves, stems, fruit peels, seeds and roots, confirmed the existence of several families of secondary metabolites of biological and pharmacological interest such as quinones and coumarins that stand out because of their significance presence. Conclusions: according to the diversity of secondary metabolites in the tested parts of Cassia uniflora Mill, as well as the biological effects reported for this species, it would be interesting to conduct new studies to find pieces of evidence on its effectiveness and safety, as a way of supporting traditional use of this plant.

Assuntos

Cassia , Larvicidas/análise , Parassimpatolíticos , Peneiramento de Líquidos

RESUMO

The antispasmodic effects of acqueous extracts (AE) and tinctures (T) of Aloysia polystachya (Griseb.) Moldenke and Aloysia gratissima (Gillies & Hook.) Tronc., Verbenaceae, were studied on rat isolated ileum and duodenum. These plants are used for gastrointestinal disorders and as eupeptic in South America. Both AE non-competitively inhibited the dose-response curves (DRC) of ACh and the DRC of Ca2+ in high-[K+]o, as well as the T. The T of A. polystachya and A. gratissima respectively inhibited the ACh-DRC at the IC50 of 3.15±0.57 and 6.46±2.28 mg leaves/mL. The Ca2+- antagonist activity of both T occurred with IC50 respectively similar to those of the ACh-DRC, and was potentiated by the depolarization produced by 10 mM TEA, a blocker of K+- channels. The spasmolytic effect of T does not involve DA release and binding to D2, since it was not reduced by 10 µ M metoclopramide. Also, T induced dose-dependent relaxation on the tonic contracture produced by high -[K+]o and ACh. By TLC there were detected in the leaves the presence of carvone, and flavonoids such as quercetin and hesperidin. By HPLC there were not found vitexin nor isovitexin, identified in A. citriodora. The monoterpene (-)- carvone non-competitively inhibited the ACh-DRC (pD'2 of 4.0±0.1) and the DRC of Ca2+ (pD'2 of 3.86±0.19), suggesting that the Ca2+- influx blockade is the mechanism of its antispasmodic effect. Results suggest that the antispasmodic effect of A. polystachya and A. gratissima are mostly explained by the non-competitive blockade of Ca+2 influx. It could be associated to the presence of flavonoids, and in the tinctures to some spasmolytic components of the essential oil such as carvone.