Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

Fitofotodermatite por Ruta graveolens com manifestação cutânea extensa / Phytophotodermatitis due to Ruta graveolens with extensive cutaneous manifestation

Dermatite de contato por planta ou fitodermatite é uma erupção cutânea resultante do contato com substâncias produzidas por diferentes espécies de vegetais. Ruta graveolens, popularmente conhecida como arruda, é uma planta da família das Rutaceae, que inclui algumas frutas cítricas, e contém inúmeras substâncias químicas fotossensíveis, incluindo os furocumarínicos. Relatamos um caso de reação de fitofototoxicidade grave em uma paciente que usou uma infusão de arruda pelas supostas qualidades ”místicas e purificadoras” da planta com extensa erupção cutânea.

Plant dermatitis or phytodermatitis is a cutaneous eruption resulting from contact with substances produced by different plant species. Ruta graveolens, popular known as common rue, is an herbal plant from the Rutaceae family, which includes the citrus fruits, and contains numerous photosensitizing substances, including furocoumarins. We report a severe case of phytophototoxicity reaction in a patient who used a common rue infusion because of its “powerful and purification” qualities.

Garden rue inhibits the arachidonic acid pathway, scavenges free radicals, and elevates FRAP: role in inflammation / 中国天然药物

AIM@#In the present study, the anti-inflammatory and antioxidant activities of the methanol extract of Ruta graveolens leaves (RG-M) were evaluated using various in vivo and in vitro models.@*METHOD@#For anti-inflammatory activity, RG-M was administered by the oral route (p.o.) in a carrageenan-induced paw edema model, and by the intraperitoneal route (i.p.) in an exudative inflammation model. In vitro inhibition of cyclooxygenase and lipoxygenase enzymes was evaluated. In vitro antioxidant activity was also examined. Endogenous antioxidant status was further evaluated by ferric reducing ability of plasma model.@*RESULTS@#RG-M showed maximum inhibition of carrageenan-induced edema (100 mg·kg⁻¹ - 33.36%; 200 mg·kg⁻¹ - 45.32% and 400 mg·kg⁻¹ - 56.28%). In the exudative inflammation model, a significant reduction in leukocyte migration (200 mg·kg⁻¹ - 54.75% and 400 mg·kg⁻¹ - 77.97%) and protein exudation (200 mg·kg⁻¹ - 31.14% and 400 mg·kg⁻¹ - 49.91%) were observed. RG-M also exhibited inhibition of COX-1 (IC50 182.27 μg·mL⁻¹) and COX-2 (IC50 190.16 μg·mL⁻¹) as well as 5-LOX (IC50 215.71 μg·mL⁻¹). Antioxidant activity was significant with improved endogenous antioxidant status.@*CONCLUSION@#The results demonstrated the anti-inflammatory and antioxidant activity of RG-M with potent inhibitory effects on the arachidonic acid pathways.

El extracto acuoso de ruta graveolens del norte de méxico causa apoptosis y muestra efecto antiproliferativo sobre el hígado de rata wistar: evidencia morfológica / Aqueous extract of ruta graveolens from the north of mexico causes apoptosis and shows antiproliferative effect on the liver of wistar rat: morphological evidence

Ruta graveolens es una planta nativa del Mediterráneo Oriental y del área Sur Occidental de Asia, de esta planta se han aislado más de 120 compuestos químicos. En un estudio previo en nuestro laboratorio se observó que un extracto acuoso de R. graveolens causó necrosis y alteraciones morfológicas sugestivas de apoptosis sobre el hígado de rata Wistar. El objetivo del presente estudio, fue evaluar la inducción de apoptosis y el posible efecto antiproliferativo in vivo de un extracto acuso de R. graveolens del norte de México, mediante métodos inmunohistoquímicos. Se utilizaron 25 ratas Wistar y se dividieron en 5 grupos (n=5). El grupo 1 correspondió al grupo control negativo, el grupo 2 o control positivo se trató con 100 mg de dexametasona/kg/día. Los grupos 3 y 4 se trataron con 30 y 100 mg de extracto de R. graveolens/kg/día respectivamente. Al grupo 5 se le administraron 100 mg de dexametasona/kg/día combinados con 100 mg de extracto de R. graveolens/kg/día. Las administraciones se realizaron vía intraperitoneal por tres días. Los animales se sacrificaron por dislocación cervical, y se tomaron muestras de hígado que se fijaron en formalina, posteriormente se incluyeron en bloques de parafina. Se obtuvieron cortes histológicos que se tiñeron con el método tricrómico de Masson. También se realizaron pruebas inmunohistoquímicas de TUNEL, anti-bcl-2 y anti-PCNA; además de un estudio morfométrico. Los resultados demuestran por primera vez el potencial apoptósico y antiproliferativo del extracto acuoso de R. graveolens del norte de México, sobre el hígado de rata Wistar. Se sugiere la posibilidad de emplear dosis menores a las administradas en este estudio del extracto acuoso de R. graveolens, para investigar su potencial uso como agente antineoplásico en estudios in vitro con líneas celulares tumorales e/o implantadas en modelos murinos de cáncer.

Ruta graveolens, is a native plant of the Eastern Mediterranean and the South Western area of Asia. From this plant, more than 120 chemical compounds have been isolated. In a previous study in our laboratory, we observed that an aqueous extract of R. graveolens, caused necrosis and morphological alterations suggestive of apoptosis on the liver of Wistar rats. The objective of this study, was to evaluate the induction of apoptosis and a possible antiproliferative effect in vivo of an aqueous extract of R. graveolens from the north of Mexico, by immunohistochemical methods. 25 Wistar rats were used and divided into 5 groups (n= 5). Group 1 corresponded to negative control group, group 2 or positive control was treated with 100 mg of dexamethasone/kg/day. Groups 3 and 4 were treated with 30 and 100 mg of extract of R. graveolens/kg/day respectively. Group 5 received the administration of 100 mg of dexamethasone/kg/day combined with 100 mg of extract of R. graveolens/kg/day. The administrations were by intraperitoneal via for three days. The animals were sacrificed by cervical dislocation, liver samples were taken, fixed in formalin and then samples were embedded in paraffin blocks. Histological sections were obtained and stained with Masson trichrome method. Immunohistochemical assays of TUNEL, anti-bcl-2, and anti-PCNA were performed. Also a morphometric study was carried out. Results show for the first time the potential apoptotic and antiproliferative effect of an aqueous extract of R. graveolens from the north of Mexico on the liver of Wistar rats. This suggests the use of lower doses of the extract of R. graveolens, to investigate its potential use as an antineoplastic agent, in studies in vitro with tumor cell lines and/or implanted in murine models of cancer.

Efecto tóxico del extracto acuoso de ruta graveolens del norte de mexico sobre el hígado de rata wistar / Toxic effect of aqueous extract of ruta graveolens from the north of mexico on the liver of wistar rat

A Ruta graveolens se le atribuyen propiedades benéficas en medicina tradicional, sin embargo se ha demostrado que también puede producir efectos adversos. A la fecha no existe evidencia que ratifique que R. graveolens es totalmente inofensiva, por este motivo el objetivo de este estudio fue determinar el efecto tóxico del extracto acuoso de las hojas de esta especie vegetal en hígado de rata. Se utilizaron 25 ratas Wistar y se dividieron en 5 grupos (n=5). El grupo 1 correspondió al grupo control negativo, el grupo 2 o control positivo se trató con 100 mg de dexametasona/kg/día. Los grupos 3 y 4 se trataron con 30 y 100 mg de extracto de R. graveolens respectivamente. Al grupo 5 se le administraron 100 mg de dexametasona/kg/día combinado con 100 mg de extracto de R. graveolens/kg/día. Las administraciones se realizaron vía intraperitoneal por tres días. Los animales se sacrificaron por dislocación cervical. Las muestras de hígado se fijaron en formalina y posteriormente se incluyeron en parafina. Se obtuvieron cortes histológicos de 5 micras de grosor que se tiñeron con Hematoxilina-Eosina para la evaluación histológica con microscopia de luz. Los resultados demuestran por primera vez que la exposición al extracto acuoso de R. graveolens induce alteraciones morfológicas en el hígado de ratas Wistar. Estas alteraciones se observaron de manera leve en el grupo 3 y se incrementaron en el grupo 4. Destacó que el mayor daño se observó en el grupo 5. Se concluye que el extracto acuoso de R. graveolens resultó tóxico, sin embargo es necesario realizar estudios adicionales con el fin de caracterizar otros efectos toxicológicos que soporten el riesgo del uso de R. graveolens en medicina tradicional a largo plazo.

In traditional medicine, beneficial properties are attributed to Ruta graveolens, but it has been shown that it can also cause side effects. Because there is no evidence that ratifies that R. graveolens is totally harmless. The aim of this study was to determine the toxic effect of aqueous extract of the leaves of this plant in rat liver. 25 Wistar rats were used and divided into 5 groups (n = 5). Group 1 corresponded to the negative control group; group 2 or positive control was treated with 100 mg of dexamethasone/kg/day. Groups 3 and 4 were treated with 30 and 100 mg of extract of R. graveolens respectively. Group 5 was treated with 100 mg dexamethasone/kg/ day in combination with 100 mg of extract of R. graveolens/kg/day. Administrations were performed intraperitoneally for three days. All animals were sacrificed by cervical dislocation. Liver samples were fixed in formalin and then embedded in paraffin. Histological sections were obtained from 5 microns thick and stained with hematoxylin-eosin for histological evaluation by light microscopy. The results demonstrate for the first time that exposure to aqueous extract of R. graveolens induces morphological changes in the liver of Wistar rats. These alterations were observed slightly in group 3. Alterations increased in group 4. Highest damage was observed in group 5. The aqueous extract of R. graveolens was toxic; furthermore additional studies are needed to characterize other toxicological effects that support the risk of use of R. graveolens in traditional medicine in a long term.

Medicinal plant extracts on the control of Diabrotica speciosa (Coleoptera: Chrysomelidae) / Extratos de plantas medicinais no controle de Diabrotica speciosa (Coleoptera: Chrysomelidae)

The aim of this study was to evaluate the insecticidal effect of aqueous, alcoholic, and oil extracts from leaves of eight medicinal plants against Diabrotica speciosa prepared at five concentrations. The extracts that used commercial soybean oil as solvent showed the highest D. speciosa mortality due to the solvent itself, regardless of the used plants and their concentrations. Thus, commercial soybean oil was discarded as solvent since at these volumes it would cause serious phytotoxicity problems. After 24 hours of exposure of the pest to the extracts, the highest D. speciosa mortality values were observed for Copaifera langsdorfii and Chenopodium ambrosioides extracts, both in 5% alcohol, and Artemisia verlotorum, in 10% water. However, in the last mortality assessment (48 h), C. langsdorfii extract in 5% alcohol showed higher mortality of this pest, followed by C. ambrosioides extract in 5% alcohol, compared to the remaining plants.

O objetivo deste trabalho foi avaliar o efeito inseticida de extratos aquosos, alcoólicos e oleosos de folhas de oito plantas medicinais contra Diabrotica speciosa preparadas em cinco concentrações. Os extratos que utilizaram óleo de soja comercial como solvente apresentaram as maiores mortalidades de D. speciosa em função do próprio óleo, independentemente das plantas utilizadas em suas concentrações. Sendo assim, o óleo de soja comercial foi descartado como solvente, pois nestes volumes acarretaria sérios problemas de fitotoxidade. Após 24 horas de exposição da praga aos extratos, os maiores valores de mortalidade de D. speciosa foram observados nos extratos de Copaifera Langsdorfii e de Chenopodium ambrosioides, ambos em álcool 5%, e de Artemisia verlotorum, em água 10%. Entretanto, na última avaliação de mortalidade (48 h), o extrato de C. langsdorfii em álcool a 5% apresentou maior mortalidade dessa praga, seguida pelo extrato alcoólico a 5% de C. ambrosioides comparada às demais plantas.

Efecto antihiperglucemiante del extracto metanólico de ruda (Ruta Graveolens) en un modelo experimental de ratas hiperglicémicas / Antihyperglycaemic Effect of the Rue (Ruta graveolens) Methanol Extract in an Experimental Model of Hyperglycemic Rats

La ruda (Ruta graveolens) es una hierba perteneciente a la familia Rutaceae, caracterizada por presentar diversas propiedades medicinales. Se ha reportado su uso como parte de la terapéutica en la Diabetes mellitus, basada en el uso de productos naturales. Se condujo una investigación con el objetivo de evaluar el efecto antihiperglucemiante de esta especie vegetal. Se emplearon 70 ratas machos a las cuales se les administró vía oral, dosis crecientes del extracto metanólico de Ruta graveolens entre 0,5 y 2 g/kg. Se incluyó un control positivo, usando glibenclamida® (500μg/kg) como agente hipoglucemiante. Se determinó la concentración de glucosa en plasma en muestras seriadas tomadas de la cola a través del método de la glucosa oxidasaperoxidasa. Se empleó jeringas de polipropileno de alta densidad y aguja de colecta simple, de uso veterinario. El extracto metanólico disminuyó la concentración de glucosa sanguínea a la dosis máxima evaluada 2,0 g/kg (<100 mg/dL). Así mismo, se identificó mediante espectrofotometría ultravioleta, los metabolitos secundarios: rutina y quercetina, los cuales pudieran contribuir a la acción hipoglucemiante. Los resultados sugieren que el extracto metanólico de la Ruta graveolens es capaz de reducir la concentración de glucosa en plasma de ratas hiperglicémicas en forma experimental, lo cual soporta su potencial uso como una alternativa de la medicina tradicional; sin embargo, deben realizarse más estudios para estimar su potencial toxicológico a dosis hipoglicemiantes.

Rue (Ruta graveolens) is an herb belonging to the Rutaceae family, characterized by various medicinal properties. Its consumption has been reported as part of therapy in diabetes mellitus, based on the use of natural products. We conducted an investigation was conducted to evaluate the antihyperglycaemic effects of this plant species. A total of 70 male rats were used which were administered orally, increasing doses of methanol extract of Ruta graveolens between 0.5 and 2 g / kg. It included a positive control, using glibenclamide ® (500μg/kg) as a hypoglycemic agent. It was later determined the plasma concentration of glucose in serial samples taken from the tail carrying out the method of glucose oxidase-peroxidase and using polypropylene syringes and needles, high-density collection simple, veterinary. The methanolic extract reduced the blood glucose concentration to the highest dose tested (2.0 g/kg <100mg/dL). Also, were identified by UV spectrophotometer secondary metabolites: routine and quercetin, which could contribute to the hypoglycemic action. The results suggest that the extract methanol of Ruta graveolens is able to reduce plasma glucose concentration in hyperglycemic rats experimentally, which supports its potential use as an alternative to traditional medicine, however, more studies should be performed to estimate its toxicological potential at hypoglycemic dose.

Efectos inducidos por Ruta graveolens L., Cnidoscolus chayamansa McVaugh y Citrus aurantium L. sobre los niveles de glucosa, colesterol y triacilglicéridos en un modelo de rata diabética / Efeitos induzidos por Ruta graveolens L., Rutaceae, Cnidoscolus chayamansa McVaugh, Euphorbiaceae, e Citrus aurantium L., Rutaceae, nos níveis de glucose, colesterol e triacilglicerídeos num modelo do rato diabético / Induced effects by Ruta graveolens L., Rutaceae, Cnidoscolus chayamansa McVaugh, Euphorbiaceae, and Citrus aurantium L., Rutaceae, on glucose, cholesterol and triacylglycerides levels in a diabetic rat model

Varias plantas con propiedades hipoglucemicas se han utilizado en medicina popular y sistemas curativos tradicionales en todo el mundo. El propósito de este trabajo fue evaluar los efectos inducidos por Ruta graveolens L., Rutaceae, Cnidoscolus chayamansa McVaugh, Euphorbiaceae, y Citrus aurantium L., Rutaceae, en un modelo de rata diabética, a la que se le cuantificaron los niveles de glucosa cada 24 horas por un mes después de la administración gástrica del extracto de las plantas. Además, el colesterol y los triglicéridos fueron evaluados usando técnicas enzimáticas. Los resultados mostraron que la administración de Cnidoscolus chayamansa a dosis de 0.5 a 1.5 g/kg induce un aumento hipoglucemico (< 200 mg/dL). Otros datos indican que Cnidoscolus chayamansa ejerce variaciones en los niveles de triacilglicéridos (80-90 mg/dL) y colesterol (88-96 mg/dL). Sin embargo, la administración de Citrus aurantium en las mismas dosis no fue suficiente para disminuir los niveles de glucosa (> 200 mg/dL). Otros resultados, mostraron que Citrus aurantium ejerce cambios en la concentración de triacilglicéridos (158-172 mg/dL) y colesterol (120-128 mg/dL). Finalmente, la administración de Ruta graveolens a dosis de 0.5 g/kg induce un efecto hipoglucemico (< 200 mg/dL). Además, Ruta graveolens a dosis de 0.5 a 1.5 g/kg induce variaciones en los niveles de triacilglicéridos (110-120 mg/dL) y colesterol (116-124 mg/dL). En conclusión la administración de Cnidoscolus chayamansa ejerce efectos hipoglucemicos en una manera dosis dependiente en comparación con Ruta graveolens y Citrus aurantium. Además, las plantas evaluadas inducen cambios en los niveles de lípidos dependiente de la dosis.

Diversas plantas com propriedades hipoglicêmicas foram usadas na medicina popular e em sistemas tradicionais de curas em torno do mundo. A finalidade deste trabalho foi avaliar os efeitos induzidos por Ruta graveolens L, Rutaceae, Cnidoscolus chayamansa McVaugh, Euphorbiaceae, e Citrus aurantium L., Rutaceae, em modelo do rato diabético onde níveis da glucose foram determinados a cada 24 h em um mês antes da administração gástrica do extrato das plantas. Colesterol e triacilglicerídeos foram avaliados usando técnicas enzimáticas. Os resultados mostraram que a administração de Cnidoscolus chayamansa a dose de 0,5 a 1,5 g/kg induz um aumento hipoglicêmico (< 200 mg/dL). Outros dados indicam que Cnidoscolus chayamansa exerce variações nos níveis de triacilglicerídeos (80-90 mg/dL) e colesterol (88-96 mg/dL). A administração de Citrus aurantium nas mesmas doses não foi suficiente para diminuir os níveis de glucose (> 200 mg/dL). Outros resultados, mostraram que Citrus aurantium exerce mudanças na concentração de triacilglicerídeos (158-172 mg/dL) e colesterol (120-128 mg/dL). Finalmente, a administração de Ruta graveolens na dose de 0.5 g/kg induziu um efeito hipoglicêmico (< 200 mg/dL). Ruta graveolens, na dose de 0.5 a 1.5 g/kg, induziu variações nos níveis de triacilglicerídeos (110-120 mg/dL) e colesterol (116-124 mg/dL). Em conclusão, a administração de Cnidoscolus chayamansa exerce efeitos hipoglicêmicos numa maneira dose dependente em comparação com Ruta graveolens e Citrus aurantium. As plantas avaliadas induzem mudanças nos níveis de lipídeos dependente da dose.

Several plants with hypoglycemic properties have been used in folk medicine and traditional healing systems around the world. The purpose of this work was to evaluate the effects of Ruta graveolens L., Rutaceae, Cnidoscolus chayamansa McVaugh, Euphorbiaceae, and Citrus aurantium L., Rutaceae, in a diabetic rat model to which the glucose levels were quantified every 24 hours by one month before of gastric administration of plants extract. Additionally, the cholesterol and triacylglycerides were evaluated using standard enzymatic techniques. The results showed that increases in the dose (0.5 to 1.5 g/kg) of Cnidoscolus chayamansa induce a high hypoglycemic effect (< 200 mg/dL). Another data indicate that Cnidoscolus chayamansa exerts variations in triacylglycerides (80-90 mg/dL) and cholesterol (88-96 mg/dL). Nevertheless, the administration of Citrus aurantium in the same doses was not sufficient for diminish the glucose levels (> 200 mg/dL). Other results, showed that Citrus aurantium exert changes in the concentration of triacylglycerides (158-172 mg/dL) and cholesterol (120-128 mg/dL). Finally, the administration of Ruta graveolens at dose of 0.5 mg/kg induces a hypoglycemic effect (< 200 mg/dL). Additionally, Ruta graveolens at dose of 0.5 to 1.5 g/kg induce variations in the triacylglycerides (110-120 mg/dL) and cholesterol (116-124 mg/dL) levels. In conclusion the administration of Cnidoscolus chayamansa it exerts hypoglycemic effects in a manner dose-dependent in comparison with both Ruta graveolens and Citrus aurantium. In addition, the plants evaluated induce changes in lipids levels dose-dependent.