Actividad antiinflamatoria y gastroprotectora del extracto acuoso de capraria biflora l / Anti-inflammatory and gastroprotective activity of the aqueous extract of capraria biflora l

Introducción: Capraria biflora L, es una planta comúnmente empleada en patologías crónicas asociadas a procesos inflamatorios. Objetivo: Evaluar el efecto antiinflamatorio y gastroprotector del extracto acuoso de Capraria biflora L. Métodos: Para el estudio de la actividad antiinflamatoria se utilizó el modelo de inflamación crónica de granulomas inducidos por discos de algodón, mientras que para la actividad gastroprotectora se evaluaron dos técnicas de producción de úlceras agudas utilizando como agentes ulcerogénicos al etanol absoluto (1mL/200g) y la Indometacina (50 mg/Kg). En el diseño experimental se utilizaron dosis de 200, 400 y 800 mg/Kg de peso. Resultados: El extracto de Capraria biflora L, presentó actividad antiinflamatoria a todas las dosis estudiadas, mostrando la dosis de 200 mg/kg resultados estadísticamente comparables a la Indometacina, mientras que las de 400 y 800 mg/kg resultaron significativamente superiores a este control. Adicionalmente se comprobó el efecto gastroprotector del extracto mediante el modelo de úlcera por etanol absoluto, a todas las dosis estudiadas, con porcientos de inhibición comparables al Omeprazol. Similares resultados se obtuvieron con el modelo de úlcera por Indometacina, siendo las dosis más efectivas las de 400 y 800 mg/Kg, con porcientos de inhibición comparables a la Ranitidina. Conclusiones: El extracto de Capraria biflora L presentó actividad antiinflamtoria y gastroprotectora bajo las condiciones evaluadas.

Anti-Inflammatory Activity and Cheminformatics Analysis of New Poten t 2-Substituted 1-Methyl-5-Nitroindazolinones.

After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. The products evaluated (3, 6, 8, 9 and 10) showed the lower values of relative leukocyte migration at 30 µM (0.14, 0.07, 0.10, 0.13 and 0.07, respectively), while in ear edema and myeloperoxidase activity methods, all the compounds reduced inflammation, only 4 and 16 yielded unsatisfactory results. The relationship linking structure and activity (SAR analysis) was determinate by using SARANEA software. The importance of the 5-Nitro group of the indazole ring for the activity was evident, and showed modest reduction when benzyl (Bn) is changed by alkyl group. A substituted Bn moiety at N2 (R) is the best substituent (5-10); nevertheless, if methylene group of Bn is deleted, the activity is affected. Also, introduction of halogen atoms mainly at positions 3 or 4 of the benzyl moiety (6 and 10) leads in general to strong activities. In fact, compounds 7 and 8 (R = 4-FBn or 4-ClBn, respectively) exhibit satisfactory results in in vivo tests and appear promising. The production of IL-6 at all doses assayed was significantly reduced, except with 16. Nonetheless, the production of TNF-α was significantly inhibited only by this chemical (16) at concentration of 50 µM. On the other hand, compound 2 was the one that mostly inhibited the expression of COX-2 and iNOS. From these results, it can be concluded that the inhibition in the release of cytokines can be one of the mechanisms of action responsible for the anti-inflammatory effect for 2-benzyl derivates while other 2-alkyl derivatives can inhibit production of NO. Therefore, nitroindazolinone chemical prototype could be an interesting structural group with anti-inflammatory purposes in the therapeutic.

Optimization and pharmacological validation of a leukocyte migration assay in zebrafish larvae for the rapid in vivo bioactivity analysis of anti-inflammatory secondary metabolites.

Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts.

Acción de un extracto acuoso de Capraria biflora L sobre la conducta en ratones NMRI / Effect of an aqucus extract of Capraria biflora L on the behaviour of NMRL mice

Se evaluó la actividad farmacológica de un extracto acuoso obtenido a partir de las hojas de Capraria biflora L, mediante los tests de Irwin y de la Curiosidad. Fueron empleados tres niveles de dosis para el caso del primer test (200,250 y 300mg/kg de peso), mientras que para el segundo se aplicó una sola dosis (250 mg/kg de peso). En el test de Irwin se observaron y evaluaron 35 parámetros, que se hallan agrupados en los aspectos de Conducta. Estado Autonómico, Estado Neurológico y otros. De estos últimos, La Conducta fue el aspecto mas afectado por el extacto (en un 90 por ciento), y en 6 parámetros del total, se encontró que su efecto es dosis-dependiente. Se obtuvo como resultado que el extracto de Capraria biflora L. posee actividad estimulante sobre el Sistema Nervioso Central a las dosis ensayadas. Paralelamente se realizó un tamizaje fitoquímicodel extracto, determinándose la presencia de alcaloides, flavonoides, saponinas, taninos, pirocatecólicos, ácidos grasos, aminoácidos y esteroides. Siendo los alcaloides y flavonoides, los metabolitos que con mayor frecuencia la literatura reporta como responsable de la actividad farmacológica de varios extractos sobre el Sistema Nervioso Central