Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite.

The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis.

Leaf essential oil of Manekia naranjoana (Piperaceae) from Costa Rica and its cytotoxic activity.

The chemical composition of the leaf oil of Manekia naranjoana (C. DC.) Callejas (Piperaceae) from Costa Rica was analyzed by capillary GC/FID and GC/MS. Fifty-five compounds were identified. Major compounds from the leaf oil were beta-pinene (30.6%), alpha-pinene (18.8%), limonene (13.7%), and beta-caryophyllene (6.1%). The oil presented very low toxicity to tumor and non-tumor cell lines, even though it contains components, such as alpha- and beta-pinene, limonene and others, which have been shown to be cytotoxic. This is the first report of the chemical composition of the essential oil obtained from this species.

Extracto y fracción alcaloidal de annona muricata con actividad de tipo ansiolítica en ratones / Anxiolytic-like effect of the extract and alkaloid fraction from Annona muricata in mice

Se evaluó el efecto neurológico ejercido por el extracto hidroalcohólico (40 por ciento) obtenido de las hojas de Annona muricata (0,5 g/kg, vo) en ratones albinos icr mediante pruebas tendientes a detectar posible actividad de tipo anticonvulsivante (electrochoquepentilentetrazol), antidepresiva (nado forzado), hipnótica (potenciación de sueño barbitúrico) y ansiolítica (laberinto en cruz). Además se examinó la unión con radioligando del extracto a receptores de benzodiazepina, se efectuó el análisis fitoquímico y a la fracción alcaloidal obtenida se le aplicó la prueba del laberinto en cruz (0,5 g/kg, vo), según los resultados previos obtenidos con el extracto. Finalmente se evaluó la toxicidad del extracto (0,1-10 mg/mL) sobre las líneas celulares ecv-304 y k562. Los hallazgos sugieren que compuestos de tipo alcaloidal presentes en Annona muricata tendrían efectos de tipo ansiolítico (53 por ciento y 58 por ciento de tiempo y frecuencia de acceso a las zonas abiertas en la prueba de laberinto en cruz elevado), no vinculados a la activación de receptores de benzodiacepinas y carentes de efectos citotóxicos in vitro. Estos datos ayudan a dar soporte al uso etnobotánico de esta especie.

The present study evaluated the neuropharmacological effect exerted by the hydroalcoholic extract (40 percent) obtained from leaves of Annona muricata (0.5 g/kg, po) in icr albino mice using tests to detect anticonvulsant (electroshock-pentylenetetrazol), antidepressant (forced swimming test), hypnotic (barbiturate sleeping time) and anxiolytic activities (elevated plus maze). The putative binding of the extract to the benzodiazepine receptor by radioligand techniques was also studied. The phytochemical analysis of the extract led to the isolation of an alkaloid fraction that was evaluated in the elevated maze test (0.5 g/kg, po), in agreement with previous results obtained with the extract. Finally, it was assessed the toxicity of the extract (0.1-10 mg/ml) in cell lines k562 and ecv-304. The results suggest that alkaloid metabolites present in Annona muricata exert anxiolytic effects (53 percent and 58 percent of the time and frequency of access to open areas in the elevated plus maze), unrelatedto the activation of benzodiazepine receptors and without cytotoxic effects in vitro. These data help support the ethnobotanical use of this plant specie.

Chemical composition of Schinus molle essential oil and its cytotoxic activity on tumour cell lines.

The leaf essential oil hydrodistilled from Schinus molle grown in Costa Rica was characterised in terms of its chemical composition, antioxidant activity, ability to induce cytotoxicity and the mechanism of cell death involved in the process. As a result, 42 constituents, accounting for 97.2% of the total oil, were identified. The major constituents of the oil were beta-pinene and alpha-pinene. The antioxidant activity showed an IC(50) of 36.3 microg mL(-1). The essential oil was cytotoxic in several cell lines, showing that it is more effective on breast carcinoma and leukemic cell lines. The LD(50) for cytotoxicity at 48 h in K562 corresponded to 78.7 microg mL(-1), which was very similar to the LD(50) obtained when apoptosis was measured. The essential oil did not induce significant necrosis up to 200 microg mL(-1), which together with the former results indicate that apoptosis is the main mechanism of toxicity induced by S. molle essential oil in this cell line. In conclusion, the essential oil tested was weak antioxidant and induced cytotoxicity in different cell types by a mechanism related to apoptosis. It would be interesting to elucidate the role that different components of the oil play in the effect observed here, since some of them could have potential anti-tumoural effects, either alone or in combination.

Estudio toxicológico y farmacológico de los extractos hidroalcohólicos de algunas especies de Smilax de Centroamérica / No disponible

Se determinó la toxicidad subcrónica y el efecto diurético, hipoglucemiante, ansiolítico y sedante de los extractos hidroalcohólicos de las raíces y rizomas Smilax engleriana, S. panamensis,S. regelii, S. subpubescens,S. kunthiiy dos quimiotipos de S. domingensis: Costa Rica (CR) y Guatemala (G). Ningún extracto resultó mortal ni causó anormalidad histológica a una dosis diaria de 2 g/kg durante 90 días, aunque algunos provocaron signos de deshidratación y disminución del peso corporal. S. panamensisy S. domingensis CR y G provocaron un efecto diurético en ratones hembra, que se mantuvo una semana después de cesar el tratamiento con S. domingensisCR y S. panamensis(efecto residual). S. engleriana y S. regelii mostraron actividad diurética, con efecto residual, en ratones machos. S. englerianamostró efecto hipoglucemiante residual en ratones machos y hembras, mientras que el extracto de S. kunthiilo mostró sólo en machos y S. panamensis y S. domingensis CR, solamente en hembras. Se observó un posible efecto ansiolítico con S. domingensis CR y S. kunthii (AU)

Subchronic toxicity and diuretic, hypoglycemic, ansiolytic and sedative effects were determined in mice after treatment with hydroalcholic extracts obtained from roots and rhizomes of Smilax engleriana, S. panamensis, S. regelii, S. subpubescens, S. kunthiiand two chemotypes of S. domingensis:Costa Rica (CR) and Guatemala (G). None of the extracts caused mortality nor histologic abnormalities at 2g/kg when given daily for 90 days. However, some extracts induced signs of dehydration and a decrease in body weight. S. panamensisand S. domingensis(CR and G) showed diuretic activity in female mice, maintaining the effect for one week after having suspended the treatment with S. domingensis CR and S. panamensis (residual effect). S. englerianaand S. regelii showed diuretic activity with a residual effect in male mice. S. engleriana induced a hypoglycaemic residual effect in female and male mice, whereas S. kunthiishowed the effect only in males and S. panamensis and S. domingensis CR only in females. A possible anxiolytic effect was observed with S. domingensisCR and S. kunthii (AU)