8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Coumarin analogue 3-methyl-7H-furo[3,2-g] chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. OBJECTIVE: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. MATERIALS AND METHODS: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. RESULTS: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. CONCLUSION: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Anti-inflammatory and antioxidant activities of Phenax rugosus (Poir.) Wedd and Tabebuia chrysanta G. Nicholson / Actividad antiinflamatoria y antioxidante de Phenax rugosus (Poir.) Wedd y Tabebuia chrysanta G. Nicholson

Inflammation is a multifactorial and highly regulated process associated to several chronic and degenerative diseases. Due to the fact that many inflammatory processes are sometimes characterized by oxidative stress, it has been demonstrated that antioxidants are useful as anti-inflammatory agents. Phenax rugosus (Poir.) Wedd and Tabebuia chrysanta G. Nicholson species are used in the Colombian region called “Eje Cafetero” due to their antiinfeccious and immunomodulatory properties. In vivo anti-inflammatory and in vitro antioxidant properties of methanolic and aqueous extracts of the previously mentioned plant species were evaluated in this research. Two acute inflammation models were used for such purpose: TPA-induced mouse ear oedema and carrageenan-induced rat paw oedema. In vitro hydroxyl, peroxyl and superoxide scavenging activity of the extracts was evaluated. The aqueous extract of Phenax rugosus was found to be promising due to its anti-inflammatory and antioxidant activities. Results obtained from this research are a support for the ethnopharmacological use of these plant species.

La inflamación es un proceso multifactorial y altamente regulado que acompaña a una gran variedad depatologías crónicas y degenerativas. Dado que muchos procesos inflamatorios crónicos se acompañan de estrés oxidativo, se ha demostrado que extractos y/o compuestos captadores de radicales libres son eficaces como antiinflamatorios. Las especies Phenax rugosus (Poir.) Wedd y Tabebuia chrysanta G. Nicholson son empleadas en la región cafetera colombiana y se les atribuyen propiedades antiinfecciosase inmunomoduladoras. En el presente estudio se evaluaron las propiedades antiinflamatorias in vivo y antioxidantes in vitro de los extractos acuosos y metanólicos de estas dos especies vegetales. Se emplearon dos modelos de inflamación aguda: edema auricular inducido por TPA en ratón y edema plantar inducido por carragenina en ratas. La actividad antioxidante in vitro se evaluó frente a los radicales hidroxilo, peroxilo y superóxido. El extracto acuoso de Phenax rugosus resultó promisorio por sus actividades antiinflamatoriay antioxidante. Estos resultados contribuyen a dar un soporte científico al uso etnofarmacológico de las dos especies vegetales estudiadas.

[Isovaleramide, an anticonvulsant molecule isolated from Valeriana pavonii]. / Isovaleramida, principio anticonvulsivo aislado de Valeriana pavonii.

INTRODUCTION: Fractioning of an extract of Valeriana pavonii, a native species used in Colombian folk medicine as tranquilizer, led to the isolation and identification of isovaleramide, one of the active constituents responsible for its central nervous system activity as anticonvulsant. OBJECTIVE: Description of the isolation and identification of isovaleramide, an active principle on central nervous system from Valeriana pavonii. MATERIALS AND METHODS: The purification of isovaleramide was carried out by chromatographic techniques. Its structural elucidation was determined by nuclear magnetic resonance and mass spectrometry. Maximal electroshock seizure was used as in vivo pharmacological test, additionally in vitro GABA-A/BDZ-binding site studies were performed. RESULTS: Isovaleramide was isolated from the most active fraction of Valeriana pavonii. This compound, at 100 mg/Kg, p.o, evidenced a 90% index protection against the maximal electroshock seizure in mice (MES), comparable to the reference agent: sodium phenytoin (20 mg/kg, p.o, 100%). In the in vitro assay, isovaleramide (300 µM) exhibited a 42% of inhibition of the binding of ³H-FNZ to its sites. CONCLUSION: Isovaleramide is one of the active anticonvulsant constituents of Valeriana pavonii, for the first time reported in this species. These results support the traditional use of Valeriana pavonii and its interest as a therapeutic source.

Isovaleramida, principio anticonvulsivo aislado de Valeriana pavonii / Isovaleramide, an anticonvulsant molecule isolated from Valeriana pavonii

Introducción. El fraccionamiento fitoquímico de Valeriana pavonii, especie vegetal nativa utilizada tradicionalmente en Colombia con fines tranquilizantes, condujo al aislamiento e identificación de la isovaleramida, uno de los principios responsables de su actividad sobre el sistema nervioso central como anticonvulsivo. Objetivo. Reportar la identificaciòn de la isovaleramida, metabolito de V. pavonii activo sobre el sistema nervioso central.Materiales y métodos. La purificaciòn de la isovaleramida se realizó mediante técnicas cromatográficas. Su estrucutra se determinó por experimentos de resonancia magnética y espectrometría de masas. Se emplearon las pruebas de convulsión máxima inducida eléctricamente en ratones como ensayo farmacológico in vivo y el ensayo in vitro de unión al sitio de las benzodiacepinas sobre el receptor GABA-A. Resultados. En el modelo de convulsión máxima inducida eléctricamente en ratones, la isovaleramida, aislada de la fracción más activa de V. pavonii, confirió un índice de protección de 90 por ciento en una dosis de 100 mg/kg, por vía oral, comparable al agente de referencia utilizado: fenitoína sódica (20 mg/kg, por ví oral, 100 por ciento) y superior al control (vehículo, 20 por ciento). En el ensayo in vitro, la isovaleramida presentó un 42 por ciento de inhibición del sitio de unión de flunitracepam con tritio. Conclusión. La isovaleramida es uno de los principios activos anticonvulsivos de V. pavonii, por primera vez reportado en esta especie. Estos resultados dan soporte al uso tradicional de V. pavonii y a su interés como fuente de principios útiles en terapéutica.

Introduction. Fractioning of an extract of Valeriana pavonii, a native species used in Colombian folk medicine as tranquilizer, led to the isolation and identification of isovaleramide, one of the active constituents responsible for its central nervous system activity as anticonvulsant. Objective. Description of the isolation and identification of isovaleramide, an active principle on central nervous system from Valeriana pavonii. Materials and methods. The purification of isovaleramide was carried out by chromatographic techniques. Its structural elucidation was determined by nuclear magnetic resonance and mass spectrometry. Maximal electroshock seizure was used as in vivo pharmacological test, additionally in vitro GABA-A/BDZ-binding site studies were performed.Results. Isovaleramide was isolated from the most active fraction of Valeriana pavonii. This compound, at 100 mg/Kg, p.o, evidenced a 90 percent index protection against the maximal electroshock seizure in mice (MES), comparable to the reference agent: sodium phenytoin (20 mg/kg, p.o, 100 percent). In the in vitro assay, isovaleramide (300 ¦ÌM) exhibited a 42 percent of inhibition of the binding of 3H-FNZ to its sites. Conclusion. Isovaleramide is one of the active anticonvulsant constituents of Valeriana pavonii, for the first time reported in this species. These results support the traditional use of Valeriana pavonii and its interest as a therapeutic source.

Antidepressant-like profile and MAO-A inhibitory activity of 4-propyl-2H-benzo[h]-chromen-2-one.

AIMS: To evaluate the central nervous pharmacological profile of 4-propyl-2H-benzo[h]-chromen-2-one (FCS-304) in ICR mice and its monoamine oxidase inhibitor activity. MAIN METHODS: FCS-304 was evaluated in screening test of central nervous system in ICR mice and against MAO activity. KEY FINDINGS: FCS-304 (25-200mg/Kg, p.o.) significantly reduced immobility time during the forced swimming test (FST) and tail suspension test (TST), but did not show effects in the rota-rod tests, maximal electroshock seizures (MES), pentylenetetrazole seizures, light-dark box, barbiturate sleeping time and cold plate tests. Furthermore, FCS-304 inhibited monoamine oxidase A (MAO-A) with IC50: 2.28+/-0.15microM, but not MAO-B. SIGNIFICANCE: These results suggest that FCS-304 could elicit antidepressant effects related to MAO-A inhibitory activity.

Efecto antinociceptivo de Critoniella acuminata, Physalis peruviana y Salvia rubescens / Antinociceptive effect of Critoniella acuminata, Physalis peruviana and Salvia rubescens

Se evaluó el efecto antinociceptivo de extractos, fracciones y compuestos de Critoniella acuminata, Physalis peruviana y Salvia rubescens mediante los métodos de placa caliente, contorsiones abdominales inducidas por ácido acético y ensayo de la formalina. La fracción de Critoniella acuminata en dosis de 100 mg/kg p.o. presentó actividad antinociceptiva al aumentar el tiempo de reacción del animal ante la aplicación de un estímulo térmico (método de la placa caliente), mientras que la fracción de Physalis peruviana, en una dosis de 100 mg/kg p. o., ejerce un efecto antinociceptivo frente al dolor generado por estímulos químicos (dolor visceral agudo) al inhibir en un 40 por ciento las contorsiones abdominales inducidas por ácido acético y el número de lamidos durante la fase ii (dolor inflamatorio agudo) en el ensayo de formalina. Estos resultados sugieren que la ayapina y la fracción de Physalis peruviana estudiadas tienen actividad antinociceptiva, con posibles mecanismos de tipo opioide y aine, respectivamente.

The antinociceptive effect of extracts, fractions and compounds of Critoniella acuminata, Physalis peruviana and Salvia rubescens were evaluated by the follow methods: Hot Plate test, acetic acid induced abdominal writhing and Formalin test. The fraction of Critoniella acuminata at doses of 100mg/kg p.o. exhibited antinociceptive effect in the hot plate test; while Physalis peruviana fraction at doses of 100 mg/kg p.o., showed an antinociceptive effect against the pain chemically induced. This fraction produced 40 percent inhibition of the acetic acid induced writhing (acute visceral nociception) and the licks during phase ii (acute inflammatory nociception)of the formalin test. The findings of this experimental study suggest that fractions of Critoniella acuminata and Physalis peruviana possess antinociceptive activity with opioid and nsaid-like mechanisms respectively.

Evaluación de actividades enzimáticas elastasa y mieloperoxidasa como marcadores de desgranulación leucocitaria en modelos de inflamación aguda / Evaluation of some enzymatic activities as markers of leukocyte degranulation in acute inflammation models

El efecto antiinflamatorio de sustancias aisladas de plantas medicinales colombianas fue evaluado mediante dos modelos de inflamación aguda: edema auricular inducido por TPA en ratón y bolsa de aire / zimosán en rata, encontrándose resultados promisorios (ej. actividades evidentes in vitro a concentración 100 M) para amarisolide, un clerodano aislado de Salvia rubescens y los glicósidos de ésteres alifáticos aislados de cálices de Physalis peruviana. Adicionalmente, se evaluó mediante métodos colorimétricos el potencial efecto inhibitorio sobre la liberación y la actividad elastasa y mieloperoxidasa (MPO), dos enzimas de desgranulación neutrofílica implicadas en procesos inflamatorios. Los resultados apuntan a que parte del efecto antinflamatorio de dichas sustancias se debe a actividad directa y/o indirecta sobre estas enzimas