Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension.

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

Atheroprotective effects of Cuphea carthagenensis (Jacq.) J. F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). MATERIAL AND METHODS: Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. RESULTS: CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. CONCLUSIONS: This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis.

Pheromones from male domestic mice influences the sexual function and gonadal steroids levels of female laboratory rats / Feromônios de influências masculinos nos ratos domésticos a função e os níveis de esteróides sexuais dos ratos de laboratório fêmeas / Feromonas de influencias masculinos en ratones domésticos la función y los niveles de esteroides sexuales en ratas hembras de laboratorio

It is well established that the behavior of different mammalians, including rodents, may undergo profound changes in the presence of individuals of other species. Therefore, the aim of this study was to verify if the presence of pheromones from male mice could influence the reproductive parameters of female rats. Twenty Swiss (SW) male mice and 16 Long Evans (LE) female Rats were housed in separate rooms, with communication in the ceiling in its entire length. A continuous flow of air was planned to pass through the room of the mice before the room of the rats and finally be exchanged with the external environment. During 45 days, vaginal smears were collected. Relative weights of reproductive organs, estradiol, progesterone, and dehydroepiandrosterone levels were also measured. The total duration of the estrous cycle and relative organ weight remained unchanged. On the other hand, the proestrus and estrus phases, as well as the estradiol levels were increased, while the diestrus phase was significantly reduced. The results have shown that maintaining LE female rats in the presence of pheromones from male SW mice can significantly change the sexual function and gonadal steroid levels.

É bem conhecido que o comportamento de diferentes mamíferos, incluindo roedores podem sofrer alterações profundas na presença de indivíduos de outras espécies. Portanto, estudamos se a presença de feromônios de camundongos machos poderiam influenciar os parâmetros reprodutivos de ratas. Vinte suíços (SW) ratos do sexo masculino e 16 Long Evans (LE) ratas foram colocadas em locais distintos, com a comunicação no teto em toda a sua extensão. Um fluxo contínuo de ar foi planejado para passar através da sala de ratinhos antes da sala de ratos e, finalmente, ser trocado com o ambiente externo. Durante 45 dias, esfregaços vaginais foram recolhidas. Os pesos relativos dos órgãos reprodutores, o estradiol, progesterona e níveis de dehidroepiandrosterona também foram medidos. A duração total do ciclo estral e peso de órgãos em relação, manteve-se inalterada. Por outro lado, as fases de proestro e estro, bem como os níveis de estradiol foram aumentadas, enquanto que a fase diestro foi reduzida significativamente. Os resultados mostraram que a manutenção de ratas LE na presença de feromônios de camundongos SW do sexo masculino pode alterar significativamente a função sexual e os níveis de esteróides sexuais.

Es bien sabido que el comportamiento de diferentes mamíferos incluyendo roedores pueden sufrir cambios profundos en la presencia de individuos de otras especies. Por lo tanto, se estudió si la presencia de feromonas de ratones machos podrían influir en los parámetros reproductivos de las ratas hembra. Veinte suizos (SW) ratones machos y 16 Long Evans (LE) ratas hembras, fueron alojados en habitaciones separadas, con la comunicación en el techo en toda su extensión. Se planificó un flujo continuo de aire para pasar a través de la habitación de los ratones antes de la habitación de las ratas y, finalmente, ser intercambiado con el ambiente externo. Durante 45 días se recogieron frotes vaginales. También se midieron los pesos relativos de los órganos reproductivos, estradiol, progesterona, y los niveles de dehidroepiandrosterona. La duración total del ciclo estral y el peso relativo de órganos se mantuvo sin cambios. Por otro lado, las fases de proestro y de estro, así como los niveles de estradiol aumentaron, mientras que la fase de diestro redujo significativamente. Los resultados han demostrado que el mantenimiento de LE en ratas hembras, con presencia de feromonas de ratones SW macho puede cambiar significativamente la función sexual y los niveles de esteroides sexuales.

Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate.

The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.

Amides from Piper as a Diuretic: Behind the Ethnopharmacological Uses of Piper glabratum Kunth.

Several species of the genus Piper are known in Brazilian folk medicine as having diuretic activity. So, we propose to investigate the acute diuretic activity and the possible toxic effects of Piper glabratum Kunth, popularly known as false Jaborandi. Additionally, we propose to check whether there is any correlation between the biological activities of the crude extract (MEPG) and its 2-methoxy-4,5-methylenedioxy-trans-cinnamoyl-pyrrolidine (MMCP) in Wistar rats. The MEPG was fractioned by chromatography column and the MMCP was identified by analyses of (1)H and (13)C RMN spectral data and correlations. Both MEPG and MMCP were assayed for diuretic activity. The preparations obtained were orally administered in a single dose to rats. The urine excretion, pH, density, conductivity, and content of Na(+), K(+), Cl(-), and HCO3 (-) were measured in the urine of saline-loaded animals. Additionally, acute toxicity of the extract was also evaluated. MMCP at doses of 30 mg/kg was able to increase the urine volume, pH, and HCO3 (-) excretion. Moreover, high dosage of MEPG showed important liver toxicity and elevated mortality when injected intraperitoneally. The results indicate that the MMCP shows important diuretic properties when administered in Wistar rats. Additionally, MEPG can induce important acute toxicity if given in high doses.

Prolonged Diuretic Activity and Calcium-Sparing Effect of Tropaeolum majus: Evidence in the Prevention of Osteoporosis.

Although several studies indicate high effectiveness in the use of the hydroethanolic extract from Tropaeolum majus (HETM) as a diuretic, the impact of its prolonged use in the presence of low estrogen levels remains unclear. Thus, the aim of this study was to investigate the diuretic effects of prolonged administration of HETM in ovariectomized rats and their interrelationship between calcium excretion and bone turnover. Forty-two female Wistar rats were ovariectomized (OVX) and treated orally with different doses of HETM (3, 30, and 300 mg/kg) for 4 weeks. On the first day of treatment and at weekly intervals for four weeks the diuretic activity was evaluated. Electrolyte concentrations and creatinine levels were estimated from urine sample of each rat. The serum lipids, urea, creatinine, and osteocalcin were also measured at the end of the experiment. The data revealed that the HETM was able to sustain its diuretic effect after prolonged treatment. Moreover, its use has not affected the urinary calcium or potassium excretion, reduces lipid levels, and maintains osteocalcin levels similarly to untreated rats. These findings support the potential of HETM as a candidate to be used in clinical conditions in which the renal loss of calcium is not desired.

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats. MATERIAL AND METHODS: The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H2O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO3(-) were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined. RESULTS: Water and Na(+) excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2',5'-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment. CONCLUSION: The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway.

Levantamento florístico do Horto Medicinal do Campus 2 da Universidade Paranaense (UNIPAR) - Umuarama/PR / Floristc survey at the Medicinal Garden at Universidade Paranaense (UNIPAR) Campus 2 - Umuarama/PR

O presente trabalho objetivou realizar o levantamento florístico do Horto Medicinal do Campus 2 da Universidade Paranaense. O levantamento foi realizado entre março de 2008 a fevereiro de 2011. Para maior precisão na coleta de dados, inicialmente toda área foi mapeada. Posteriormente, de acordo com o ciclo reprodutivo, os espécimes foram coletados e herborizados segundo técnicas usuais preconizadas para a taxonomia. A identificação botânica foi realizada por meio do envio de material aos taxonomistas, bem como por estudos de comparação à literatura especializada e por comparações com exsicatas do Herbário da Universidade Estadual de Maringá (HUEM). As espécies foram depositadas no Herbário Educacional da Universidade Paranaense (HEUP). Os resultados demonstraram a ocorrência de 332 espécies, pertencentes a 256 gêneros e 89 famílias. As famílias de maior destaque em número de espécies foram: Asteraceae (11,3%), seguida de Lamiaceae (6,2%) e Euphorbiaceae (5,3%). Quanto ao hábito, as herbáceas totalizaram 41,6%, seguida das arbóreas (19,6%), arbustivas (16,5%), subarbustivas (15,1%) e lianas (7,2%). As exóticas (65,3%) foram mais representativas que as nativas (34,7%). No presente estudo, as espécies pertencentes às famílias Asteraceae, Lamiaceae e Euphorbiaceae foram os grupos predominantes encontrados em nossa pesquisa, esses dados mostram a importância dessas famílias como espécies medicinais como relatado pela literatura. O alto índice de espécies herbáceas encontradas no estudo é uma consequência do grande número de espécies pertencentes a estas famílias. Conclui-se que o Horto Medicinal do Campus 2 da UNIPAR, apresenta uma grande diversidade de espécies.

The aim of this study was to survey the flora of the Medicinal Garden at the Universidade Paranaense (UNIPAR) Campus 2. The survey was carried out between March 2008 and February 2011. In order to increase accuracy in data collection, the garden area was entirely mapped. Later, according to the reproductive cycle, specimens were collected and processed using current techniques applied in botanical taxonomy. Botanical identification was performed by sending materials to taxonomists, as well as by comparison studies using specialized literature and comparison with exsiccate from the State University of Maringa Herbarium (HUEM). The species were deposited in the Teaching Herbarium at Universidade Paranaense (HEUP). The results demonstrated the occurrence of 332 species belonging to 256 genera and 89 families. The most representative families considering their number of species were Asteraceae (11.3%), followed by Lamiaceae (6.2%) and Euphorbiaceae (5.3%). According to the plant life form, herbs totaled 41.6%, followed by arboreous (19.6%), shrubs (16.5%), subshrubs (15.1%) and climbing plant (7.2%). Exotic plants (65.3%) were more frequent than native species (34.7%). In the present study, species belonging to Asteraceae, Lamiaceae and Euphorbiaceae families were the most predominant groups found; these data show the importance of these families as medicinal species, as reported in literature. The high index of herbaceous species found in the study is a consequence of the great number of species belonging to these families. Based on these results, it can be concluded that the Medicinal Garden at UNIPAR Campus 2 presents a great diversity of species, with predominance of herbs.

Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro. RESULTS: HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ. CONCLUSION: Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.

Atividade de tropaeolum majus l. sobre a mobilização e migração leucocitária em modelo de bolsão inflamatório / Activity of tropaeolum majus l. on the mobilization and leukocyte migration in an air pouch model

Tropaeolum majus L. (Tropaeolaceae) é uma importante planta medicinal conhecida popularmente no Brasil como chaguinha, capuchinha ou nastúrcio. Toda parte aérea da planta tem sido utilizada há séculos pela medicina popular. Suas folhas secas ou em infusão são usadas popularmente para o tratamento de várias doenças, incluindo processos inflamatórios. O objetivo do presente estudo foi avaliar o perfil da migração leucocitária em vigência de resposta inflamatória aguda, após um tratamento subcrônico com T. majus. Para isto, ratos Wistar machos foram tratados por cinco dias com três diferentes doses do extrato hidroetanólico (EHTM) obtido de T. majus (75, 150 e 300 mg/kg). Os animais controle receberam volume equivalente de solução salina (5,0 ml/kg) ou indometacina (5,0 mg/kg). Durante este período, os animais receberam 10 ml de ar estéril na cavidade subcutânea (air pouch) em três dias alternados. No quinto dia, uma hora após os tratamentos, a resposta inflamatória foi induzida com a administração de 1 ml de carragenina (solução 1%) na cavidade subcutânea, e 6 horas após, amostras de sangue e do exsudato foram coletadas para a determinação de leucócitos totais e para a realização da contagem diferencial. Os resultados demonstraram que a indometacina reduziu o número de leucócitos totais para o exsudato em aproximadamente 65%. O EHTM nas doses de 75 e 300 mg/kg também reduziram significativamente a migração destas células, com valores estimados em 23 e 40%, respectivamente. Estes resultados indicam uma possível atividade anti-inflamatória do T. majus neste modelo experimental, justificando, pelos menos em parte, o uso popular desta espécie.

Tropaeolum majus L. (Tropaeolaceae) is an important medicinal plant popularly known in Brazil as chaguinha, capuchinha or nasturtium. This species has been used for centuries in popular medicine. Dried leaves are popularly used in infusion for the treatment of various diseases, including inflammatory processes. The aim of this study was to assess the profile of leukocyte migration during an acute inflammatory response after a subchronic treatment with T. majus. For this purpose, male Wistar rats were treated for five days with three different doses of hydroalcoholic extract (HETM) obtained from T. majus (75, 150 and 300 mg/kg). Control animals received equivalent volume of saline solution (5.0 ml/kg) or indomethacin (5.0 mg/kg). During this period, the animals received 10 ml of sterile air in the subcutaneous cavity (air pouch) on three alternate days. On the fifth day, one hour after treatment, the inflammatory response was induced by administration of 1 ml carrageenan solution (1%) in the subcutaneous cavity, and 6 hours after, blood and exudate samples were collected for determination of total and differential leukocytes. The results showed that indomethacin reduced leukocyte migration in the exudates to about 65%. The HETM at doses of 75 and 300 mg/kg also significantly reduced the migration of these cells, with values ??of 23 and 40%, respectively. These results indicate a possible anti-inflammatory activity of T. majus in this experimental model, explaining, at least in part, the popular use of this species.