Foeniculum vulgare Mill. inhibits lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

@# Objective: To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide (LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in mice. Methods: LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species (ROS) was studied using DCF-DA assay. The antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western blotting. For in vivo testing, LPS (1 mg/kg, i.p. ) was given daily for five days in male Swiss albino mice to produce chronic neuroinflammation. Cognitive and behavioral tests were performed using open-field, passive avoidance, and rotarod experiments in LPS-induced mice. Results: Foeniculum vulgare extract (25, 50 and 100 μg/mL) significantly attenuated the LPS-activated increase in nitric oxide (NO), ROS, cyclooxygenase-2, inducible NO synthase, IL-6, and TNF-alpha (P < 0.05). Moreover, LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract (P < 0.05). The extract also regulated the NF-κB/MAPK signaling in BV-2 cells. In an in vivo study, Foeniculum vulgare extract (50, 100, and 200 mg/kg) markedly mitigated the LPS-induced cognitive and locomotor impairments in mice. The fingerprinting analysis showed distinctive peaks with rutin, kaempferol-3-O-glucoside, and anethole as identifiable compounds. Conclusions: Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

Floating tablets of hydralazine hydrochloride: optimization and evaluation

Hydralazine hydrochloride has a half-life of 2 to 4 hours with an oral bioavailability of 26-50%. Since hydralazine has a demethylating effect on various suppressor genes, it can be used in various types of cancer to support chemotherapy. The purpose of this study was to optimize and evaluate floating tablets of hydralazine hydrochloride designed to prolong the gastric residence time and to provide controlled release of the drug for 14 h. The floating tablets of hydralazine hydrochloride were prepared by the wet granulation method. Semi-synthetic polymers of hydroxy propyl methyl cellulose (HPMC K100M) and ethyl cellulose were used as the release retarding agents. A 2² factorial design was applied to systematically optimize the drug release profile. The concentrations of HPMC K100M and ethyl cellulose were optimized to provide controlled release of hydralazine for 14h. Non-Fickian diffusion release transport was confirmed as the release mechanism for the optimized formulation and the predicted values agreed well with the experimental values. Drug excipient compatibility studies were investigated by FTIR, DSC and XRD. These data indicate that there were no chemical interactions between the drug and the polymer. In vivo X-ray imaging showed floating tablet performance in rabbits.

O cloridrato de hidralazina apresenta meia-vida de 2 a 4 horas, com biodisponibilidade oral de 26-50%. Uma vez que a hidralazina possui efeito desmetilante em vários genes supressores, ela pode ser utilizada para diversos tipos de câncer, em apoio à quimioterapia. O objetivo deste estudo foi o de avaliar e otimizar comprimidos flutuantes de cloridrato de hidralazina, planejados para prolongar o tempo de residência gástrica e proporcionar liberação controlada do fármaco por 14 h. Os comprimidos flutuantes de cloridrato de hidralazina foram preparados pelo método de granulação úmida. Polímeros semi-sintéticos de hidroxipropiletil celulose (HPMCK100M) e acetato de celulose foram utilizados como agente de retardamento de liberação. Aplicou-se planejamento fatorial 2² para otimizar sistematicamente o perfil de liberação do fármaco. As concentrações de HPMCK100M e de etilcelulose foram otimizadas para se obter liberação controlada de hidralazina durante 14 h. O transporte de liberação de difusão não-Fickiana foi confirmado como o mecanismo de liberação para a formulação otimizada e os valores previstos estiveram de acordo com os valores experimentais. Estudos de compatibilidade entre fármaco e excipiente foram realizados por FTIR, DSC e DRX. Estes dados indicaram que não havia interação química entre o fármaco e o polímero. Imagens de raios-X in vivo mostraram o desempenho dos comprimidos flutuantes em coelhos.