RESUMEN
The herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) occur worldwide. Infections caused by these viruses have great public health importance due to the growing resistance to the first-choice drug, acyclovir, especially in immunosuppressed patients. Alkaloids derived from species of Annonaceae have been reported as antiviral agents against HSV and others viruses. Within this context, we evaluated the antiviral activity of the total alkaloid fraction (TAF) extracted from the branches of Fusaea longifolia (Aubl.) Saff. (Annonaceae), a species native to the Amazon region, against the HSV-1 and HSV-2 viruses. The antiviral activity was evaluated through the plate reduction assay and the mode of action was investigated by a set of other assays. The TAF was active against the HSV-2 strain 333 and against the HSV-1 strains KOS and 29R (acyclovir resistant), with selectivity index values (SI = 50% cytotoxic concentration/50% effective concentration) of 5, 4 and 3, respectively. In the preliminary study of the anti-HSV-2 mode of action, TAF showed viral inhibitory effects if added up to 12 h post-infection, had virucidal activity and did not present viral inhibition in pre-treatment. Our results showed that the TAF exhibited anti-HSV activity. Regarding HSV-2, TAF acted after the viral infection and had virucidal activity. A mass spectrometry analysis revealed the presence of nine alkaloids in the TAF that had previously been reported for Annonaceae, including liriodenine, lysicamine and isoboldine, which have been described as potential anti-HSV-1 agents.(AU)
Os vírus herpes simplex tipo 1 (HSV-1) e tipo 2 (HSV-2) têm ampla ocorrência global. As infecções causadas por esses vírus têm grande importância em saúde pública devido à crescente resistência ao fármaco de primeira linha, aciclovir, principalmente em pacientes imunossuprimidos. Alcaloides derivados de espécies de Annonaceae têm sido relatados como agentes antivirais contra o HSV e outros vírus. Neste contexto, nós avaliamos a atividade antiviral da fração alcaloide total (TAF) dos ramos de Fusaea longifolia (Aubl.) Saff. (Annonaceae), uma espécie nativa da região amazônica, contra os vírus HSV-1 e HSV-2. A atividade antiviral foi avaliada através do ensaio de redução em placa e o modo de ação foi investigado por um conjunto de ensaios. O TAF foi ativo contra a cepa HSV-2 333 e contra as cepas HSV-1 KOS e 29R (resistente ao aciclovir), com valores de índice de seletividade (IS = 50% concentração citotóxica/50% concentração efetiva) de 5, 4 e 3, respectivamente. No estudo preliminar do modo de ação da atividade anti-HSV-2, o TAF inibiu a replicação viral quando adicionados até 12 h pós-infecção, apresentou atividade virucida e não apresentou inibição viral no pré-tratamento. Nossos resultados mostraram que o TAF exibiu atividade anti-HSV. Em relação ao HSV-2, o TAF atuou após a infecção viral e apresentou atividade virucida. Uma análise do TAF por espectrometria de massas identificou a presença de nove alcaloides, incluindo liriodenina, lisicamina e isoboldina, que já foram descritos como potenciais agentes anti-HSV-1.(AU)
Asunto(s)
Simplexvirus/inmunología , Annonaceae/virología , Alcaloides/efectos adversos , Antivirales/químicaRESUMEN
Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.
Asunto(s)
Análisis Espectral/métodos , Microscopía Electrónica de Rastreo/métodos , Piper nigrum/efectos adversos , Tracto Gastrointestinal/anomalías , Composición de Medicamentos/instrumentación , Comprimidos/clasificación , Técnicas In Vitro/métodos , Alcaloides/efectos adversos , Medicina Tradicional/instrumentación , Antioxidantes/efectos adversosRESUMEN
Resumen Nicotiana glauca también llamada Palán Palán, es un arbusto con hojas verdes azuladas y despulidas y una flor amarilla tubular pendulante que presenta alcaloides piridínicos, como nicotina, nornicotina, anatabina y anabastina (análogo estructural de la Nicotina). Se presenta el caso clínico de una paciente de 50 años con cuadro agudo de debilidad muscular generalizada que evoluciona con paro respiratorio, tras la ingesta accidental de una cantidad desconocida de hojas de Nicotiana glauca, cultivadas en una huerta hogareña mediante técnica de hidroponía y confundidas por su conviviente con espinaca. Presentó aumento de lactato y Troponina Ultra Sensible e Hipoquinesia Global de Ventrículo Izquierdo en el ecocardiograma, compatible con Aton tamiento Miocárdico (AM), que evolucionó favorablemente. Si bien hay pocos reportes, se han informado muertes de animales y humanos, tras la ingesta accidental de Nicotiana glauca. El inicio del cuadro es rápido, con patrón bifásico, con vómitos y estímulo simpático, seguido por bloqueo ganglionar y neuromuscular, pudiendo presentar paro respiratorio, shock, convulsiones y coma. El AM es una disfunción miocárdica prolongada con retorno gradual de la actividad contráctil, posterior a un episodio breve de isquemia grave, puede ser asintomático, pudiendo presentar alteraciones en el electrocardiograma, enzimas cardíacas o ecocardiograma. Generalmente presenta pronóstico favorable, pudiendo presentar insuficiencia cardíaca ante patologías concurrentes o aumento de requerimientos de oxígeno.
Abstract Nicotiana glauca is a shrub with bluish green leaves and a pendulous tubular yellow flower. It has pyridine alkaloids, such as nicotine, nornicotine, anatabine and anabastine (structural analog of Nicotine). We present the case of a 50 years old pa- tient with acute generalized muscle weakness that evolves to respiratory arrest, after accidentally ingesting an unknown quantity of Nicotiana glauca leaves, grown in a home vegetable garden, using a hydroponic technique and confused by her cohabiting with spinach. She presented increased lactate and Ultra Sensitive Troponin and Left Ventricular Global Hypokinesia in the echo- cardiogram, compatible with Myocardial Stunned, that it evolved favorably. There are few reports, animal and human deaths have been reported following accidental ingestion of Nicotiana glauca. The onset of the symptoms is early, with a biphasic pattern, with vomiting and sympathetic stimulation, followed by ganglionic and neuromuscular blockage and may present respiratory arrest, shock, seizures and coma. Myocardial Stunned is a prolonged myocardial dysfunction with gradual return of contractile activity after a brief episode of severe ischemia, it can be asymptomatic, and it can present alterations in the electrocardiogram, cardiac enzymes or echocardiogram. Generally presents a benign prognosis, being able to present heart failure with concurrent patholo- gies or increased requirements.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Intoxicación/complicaciones , Intoxicación/diagnóstico , Intoxicación/terapia , Nicotiana/efectos adversos , Aturdimiento Miocárdico/epidemiología , Alcaloides/efectos adversos , Alcaloides/farmacología , Intoxicación/epidemiología , Nicotiana/anatomía & histología , Alcaloides/clasificaciónRESUMEN
Malt is the mature fruit of Hordeum vulgare L. after germination and drying and has been applied for treatment female abnormal galactorrhea. Previous studies have showed total alkaloids in malt have anti-HPRL effect. However, total alkaloids of malt change with the growth cycle, and the specified levels of total alkaloids in different bud length of malt have not been decided. To determine the definitive level of total alkaloids in different buds of malt and the most suitable bud length for clinical application by comparing effects on hyperprolactinemia rat. During the budding of malt, the content of total alkaloids first increased and then decreased, and it peaked at a bud length of 0.75 cm. Treated the HPRL model rats with different buds of malt, the PRL level was decreased, the number of PRLpositive cells and the mRNA expression level in the pituitary were significantly declined, and the number of dopamine D1 and D2 receptors in the hypothalamus was increased. The above changes were most significant in 0.75 cm bud. These results suggest that in terms of the content of effective substance and the effects on HPRL model rats, a malt bud length of 0.75 cm is optimal for clinical application.
Asunto(s)
Animales , Femenino , Ratas , Hordeum/clasificación , Benchmarking/métodos , Plantones/efectos adversos , Hiperprolactinemia/clasificación , Dopamina , Germinación , Alcaloides/efectos adversos , Sistema Endocrino/anomalías , FrutasRESUMEN
Feedlot cattle is submitted to a diet rich in energy and reduced in fibres that induces the sub-acute ruminal acidosis (SARA) with its lesions and clinical signs. Recent studies have demonstrated some amelioration of this condition by the use of isoquinolone alkaloids found in Macleaya cordata (Papaveraceae) such as Sanguinarine and Chelerythrine. These compounds have demonstrated antimicrobial, antiinflammatory and immune-modulatory effects in both humans and animals The aim on this study, using histopathology and a score system, was to evaluate the differences between a non-treated and a treated group feed with these alkaloids, present in trade preparation Sangrovit-RS® as a source of sanguinarine (SG), chelerythrine (CH) and protropine (PA) standardized to 0.15% w/w SG, using feedlot cattle under a high-grain diet as an inflammatory model for gastrointestinal system. The samples of forestomachs were evaluated and graded using scores ranging from zero (0) to three (3) obtained at light-microscopic fields of 400X. Parameters such as inflammation, hydropic degeneration, hyperkeratosis, and vesicle formation were accessed in the different layers of the tissues, considering the severity and dispersion of the microscopic lesions. The soft tissues such as the abomasum, small intestine, cecum and colon had their total amount of inflammatory cells counted at light-microscopic fields of 200X. The rumen of the SG-CH-PRO-treated group showed a significant reduction in the epithelial hydropic degeneration scores (p ≤ 0.001) and lamina propria inflammation (p ≤ 0.001).The reticulum had a similar reduction in scores of epithelial (p ≤ 0.002) and stratum corneum hydropic degeneration (p ≤ 0.001), hyperkeratosis (p ≤ 0.002) and inflammation in lamina propria (p ≤ 0.001) and epithelium (p ≤ 0.002). The omasum had no significant differences. All non-keratinized tissues, except for ileum, had a significant decrease (p ≤ 0.001) in the total counting of inflammatory cells. In this trial, the feedlot cattle feed with high grain diet and treated with isoquinolone alkaloids expressed lesions that indicate ameliorations and worsening's. Ameliorating effects of the alkaloids were better demonstrated in tissues with reduced or no corneal layer in the mucosa and in the absence of a lipopolysaccharides rich acidic environment reinforcing the notion of the topic action, the dependence of the media pH and the time of exposure modulating the pharmacological mechanisms of these alkaloids. The observed cytolytic (oncolysis) effect in epithelial forestomachs cells under low pH values, worsening the osmotic status, should be considered before clinical applications.(AU)
As dietas para bovinos confinados possuem alta quantidade de alimentos energéticos com menor quantidade de alimentos volumosos (fibras), favorecendo a indução de acidose ruminal subaguda com formação de lesões gastrointestinais e sintomas clínicos deletérios. Recentes trabalhos têm demonstrado alguma amenização desta condição pelo uso de alcaloides isoquinolínicos encontrados na Macleaya cordata (Papaveraceae) tais como a sanguinarina e a cheleretrina, os quais tem demonstrado efeitos anti-inflamatórios, antimicrobianos e imuno modulatórios em humanos e animais. O objetivo deste estudo foi, através da histopatologia e de um sistema de escores, avaliar as diferenças entre um grupo não tratado e um grupo tratado com alcaloides isoquinolínicos, presentes na formulação Sangrovit RS® como fonte de sanguinarina (SG), chelerethrina (CH) and protropina (PA) padronizadas em 0,15 % w/w SG, usando bovinos em confinamento recebendo uma dieta rica em grãos como modelo inflamatório para o sistema gastrointestinal. Amostras dos pré-estômagos foram avaliadas por escores variando de zero a três, obtidos por microscopia de luz em diferentes campos em aumentos de 400X. Inflamação, degeneração hidrópica, hiperqueratose e formação de vesículas foram avaliadas nas diferentes camadas dos pré-estômagos tendo em vista a intensidade e a extensão das lesões. Tecidos não queratinizados como abomaso e intestino delgado, ceco e cólon tiveram seu total de células inflamatórias contadas por microscopia de luz em diferentes campos com aumentos de 200X. No rumem do grupo tratado houve uma redução significante no número de campos contendo degeneração hidrópica epitelial (p ≤ 0,001) e inflamação de lâmina própria (p ≤ 0,001). O retículo teve uma redução similar nos escores scores de degeneração hidrópica epitelial (p ≤ 0.002), degeneração hidrópica no estrato córneo (p ≤ 0.001), hiperqueratose (p ≤ 0.002) e inflamação na lamina própria (p ≤ 0.001) e inflamação epitelial (p ≤ 0.002). Não foram encontradas diferenças significantes no omaso. Todos os tecidos não queratinizados, exceto pelo íleo, tiveram uma redução significativa (p ≤ 0.001) no total de células inflamatórias. Neste experimento, bovinos em confinamento recebendo dieta rica em grãos e tratados com alcaloides isoquinolínicos tiveram lesões que tiveram melhoras e pioras. Os efeitos de melhora foram melhor demonstrados em tecidos sem camada córnea e na ausência de um meio ácido rico em lipopolisacarídeos, reforçando a noção da ação tópica, da dependência do pH do meio e do tempo de exposição modulando os mecanismos farmacológicos destes alcalóides. O efeito citolítico (oncólise) sobre células epiteliais de pré-estômagos em baixos valores de pH, piorando o estado osmótico das células, deveria ser considerado antes das aplicações clínicas.(AU)
Asunto(s)
Animales , Acidosis/tratamiento farmacológico , Bovinos , Alcaloides/efectos adversos , Gastroenteritis/tratamiento farmacológico , Tracto Gastrointestinal/lesionesRESUMEN
This study examined the effects of purmorphamine and cyclopamine, classical agonists and inhibitors of the Hedgehog (Hh) signaling pathway, in the adipogenic differentiation of porcine adipose-derived mesenchymal stem cells (AMSC) to investigate the roles underlying adipogenic differentiation in AMSC. Porcine-derived AMSC were established, and the Hh signaling pathway was activated or inhibited by treatment with purmorphamine or cyclopamine. The adipogenic differentiation of the porcine AMSC was then analyzed by Oil Red O staining. The expression levels of Hh signaling pathway factors and adipogenic transcription factors were determined using quantitative real-time polymerase chain reaction and western blot analysis. We verified that the expression levels of positive regulators of the Hh pathway (Smo, Gli1, Gli2, and Gli3) decreased during adipogenesis, whereas those of negative regulators (Ptc1 and Ptc2) increased. Purmorphamine can inhibit the adipogenic differentiation of porcine AMSC in vitro culture. In addition, both the expression of the CCAAT/enhancerbindingprotein-α and that of the peroxisome proliferator-activated receptor-γ decreased in the presence of purmorphamine. By contrast, cyclopamine had no significant effect on the adipogenic differentiation of porcine AMSC. The Hh signaling pathway inhibits the adipogenic differentiation potential of porcine AMSC.(AU)
Asunto(s)
Animales , Porcinos/genética , Alcaloides/efectos adversos , Adipogénesis/fisiología , Proteínas Hedgehog/efectos adversos , Células Madre Mesenquimatosas/fisiología , Tejido AdiposoRESUMEN
Choisya 'Aztec-Pearl', a hybrid of Choisya ternata and Choisya dumosa var. arizonica, had the antinociceptive activity in the ethanol extract (EECA) of its leaves evaluated. Two quinoline alkaloids, anhydroevoxine (A) and choisyine (C), isolated from these leaves were also tested. The results obtained pointed out to a very high antinociceptive activity measured by the hot plate model for EECA (at doses of 10, 30 and 100 mg/kg) as well as for A and C (at doses of 1, 3 and 10 mg/kg). The magnitude of the activity was two-fold higher than the one observed for the morphine treated animals for the higher doses of extracts/compounds (30, 100 mg/kg and 3, 10 mg/kg respectively). The mechanism of action for this activity was also investigated and it seems that for EECA as well as A and C, the opiate system plays an important role. Results have also shown that the nitric oxide (NO) system also play a pivotal role in the case of EECA and A while for C it seems that the cholinergic system have some involvement. The acute toxicity was evaluated for EECA with results showing no important toxic effect.
Asunto(s)
Alcaloides/aislamiento & purificación , Analgésicos/farmacología , Extractos Vegetales/farmacología , Quinolinas/aislamiento & purificación , Rutaceae/química , Alcaloides/efectos adversos , Alcaloides/farmacología , Analgésicos/efectos adversos , Animales , Masculino , Ratones , Extractos Vegetales/efectos adversos , Quinolinas/efectos adversos , Quinolinas/farmacologíaRESUMEN
Many natural substances with proven anti-inflammatory activity have been isolated throughout the years. The aim of this review is to review naturally sourced alkaloids with anti-inflammatory effects reported from 2000 to 2010. The assays were conducted mostly in vivo, and carrageenan-induced pedal edema was the most used experimental model. Of the 49 alkaloids evaluated, 40 demonstrated anti-inflammatory activity. Of these the most studied type were the isoquinolines. This review was based on NAPRALERT data bank, Web of Science and Chemical Abstracts. In this review, 95 references are cited.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios no Esteroideos/farmacología , Mediadores de Inflamación/farmacología , Extractos Vegetales/farmacología , Alcaloides/efectos adversos , Alcaloides/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Isoquinolinas/efectos adversos , Isoquinolinas/farmacología , Isoquinolinas/uso terapéutico , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéuticoRESUMEN
After consumption of a new taste, there are mainly two possible outcomes for the establishment of a taste memory, either it will be aversive or safe depending on the consequences of taste consumption. It has been proposed that both types of learning share a common initial taste memory trace, which will lead to two different memory traces, safe or aversive. To study the role of PKC activity in aversive or safe taste memory formation, we administered chelerythrine, a PKC inhibitor, into the insular cortex or parietal cortex 20 min before conditioned taste aversion or attenuation of neophobia training. The results suggest that PKC activity is needed in the insular cortex for the establishment of aversive taste memory, but not for safe taste memory.