RESUMO
The introduction of glucagon-like peptide 1 (GLP-1)-based therapies has greatly improved the management of type 2 diabetes (T2D), as they ensure good blood glucose control and promote weight loss. Ingestion of standardized herbal remedies that promote the same endogenous metabolic processes affected by the GLP-1-based treatments could provide cheaper alternatives in low- and middle-income countries, where there is currently an increase in the incidence of T2D. The focus in this study was to determine quality control parameters and the prime factors for the Rauvolfia-Citrus tea (RC-tea), as used in Nigerian traditional medicine to treat T2D. We have previously shown that the RC-tea that is made by boiling leaves of Rauvolfia vomitoria Afzel. and fruits of Citrus aurantium L. causes normalization of blood glucose and reduction of ectopic lipid accumulation in genetic diabetic (BKS-db) mice and in humans with T2D. The standardized RC-tea was made by boiling 40 g dried R. vomitoria foliage and 200 g fresh C. aurantium fruits per litre. The resulting golden-brown extract is free of microbial contamination, has pH 5 and contains ca. 230 mg naringin (marker compound for C. aurantium) and 25 mg robinin (marker compound for R. vomitoria) per litre. In addition, the herbal extract has the characteristic HPLC-DAD fingerprint where the marker compounds, naringin and robinin have retention times of approximately 26.3 min and 26.9 min, respectively, when using the outlined column and gradient elution conditions. Comparative evaluations of the antidiabetic effects of the standardized RC-tea and boiling water-extracts made with C. aurantium fruits alone (CA), R. vomitoria foliage alone (RV) and a combination of CA and RV, (CA + RV) in BKS-db mice, indicate that components from R. vomitoria foliage drive the reductions in ectopic lipid accumulation, since CA-treated mice lacked this effect. However, the normalization of blood glucose arises from combination of components from the two source plant materials as administration of either CA or RV resulted in hypoglycaemia. Interestingly, treatment with the CA + RV mixture, generated by mixing individually produced CA and RV plant extracts, resulted in hyperglycaemia, possibly due to drug-drug interactions of the blood glucose-reducing components in either plant extract. Hence, our data show that the best antidiabetic outcome results from the traditional practice of boiling R. vomitoria foliage and C. aurantium fruits together.
Assuntos
Citrus , Diabetes Mellitus Tipo 2 , Flavanonas , Hipoglicemiantes , Extratos Vegetais , Folhas de Planta , Rauwolfia , Animais , Hipoglicemiantes/farmacologia , Citrus/química , Camundongos , Flavanonas/farmacologia , Folhas de Planta/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Rauwolfia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Nigéria , Medicinas Tradicionais Africanas , Masculino , Glicemia/efeitos dos fármacos , Controle de QualidadeRESUMO
BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the digestive tract. Rauwolfia polysaccharide (Rau) has therapeutic effects on colitis in mice, but its mechanism of action needs to be further clarified. In the study, we explored the effect of Rau on the UC cell model induced by Lipopolysaccharide (LPS). METHODS: We constructed a UC cell model by stimulating HT-29 cells with LPS. Dextran sodium sulfate (DSS) was used to induce mice to construct an animal model of UC. Subsequently, we performed Rau administration on the UC cell model. Then, the therapeutic effect of Rau on UC cell model and was validated through methods such as Cell Counting Kit-8 (CCK8), Muse, Quantitative realtime polymerase chain reaction (RT-qPCR), Western blotting, and Enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that Rau can promote the proliferation and inhibit the apoptosis of the HT-29 cells-induced by LPS. Moreover, we observed that Rau can inhibit the expression of NOS2/JAK2/STAT3 in LPS-induced HT-29 cells. To further explore the role of NOS2 in UC progression, we used siRNA technology to knock down NOS2 and search for its mechanism in UC. The results illustrated that NOS2 knockdown can promote proliferation and inhibit the apoptosis of LPS-induced HT-29 cells by JAK2/STAT3 pathway. In addition, in vitro and in vivo experiments, we observed that the activation of the JAK2/STAT3 pathway can inhibit the effect of Rau on DSS-induced UC model. CONCLUSION: In short, Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway. This study provides a theoretical clue for the treatment of UC by Rau.
Assuntos
Alcaloides , Colite Ulcerativa , Colite , Rauwolfia , Animais , Camundongos , Alcaloides/farmacologia , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Polissacarídeos/metabolismoRESUMO
Rauvolfia tetraphylla is an essential medicinal plant that has been widely used in traditional medicine for various disease treatments. However, the tumor suppressor activity of R. tetraphylla and its phytocompounds were not explored against triple-negative breast cancer. The current research investigated the impact of R. tetraphylla methanolic extract (RTE) and its isolated compounds Ajmaline (RTC1) and Reserpine (RTC2) on triple-negative breast cancer cell line (MDA-MB-231) focusing on anti-proliferative effects. Our study imparts that RTE and RTC2 showed promising cytotoxic effects compared to RTC1. So further experiments have proceeded with RTE and RTC2, to evaluate its proliferation, migration, and apoptotic effect. The result shows around 80% of cells were observed in the G0/G1 phase in cell cycle analysis indicating the cell cycle inhibition and duel staining clearly showed the apoptotic effect. The migration of cells after the scratch was 60.45% observed in control and 90% in treated cells showing the inhibition of migration. ROS distribution was intense compared to control indicating the increased ROS stress in treated cells. Both RTE and RTC2-treated cells showed the potential to suppress proliferation and induce apoptotic change by upregulating BAX and MST-1 and suppressing Bcl2, LATS-1, and YAP, proving that deregulation of YAP resulting in the blockage of TEAD-YAP complex and inhibit proliferation. Therefore, R. tetraphylla extract and its isolated compounds were demonstrated to find its ability to act against MDA-MB-231 and these findings will help adjudicate it as a therapeutic drug against experimental triple-negative breast cancer.
Assuntos
Neoplasias da Mama , Rauwolfia , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Rauwolfia/metabolismo , Via de Sinalização Hippo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Apoptose , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proliferação de CélulasRESUMO
Besides tryptamine (1) and secologanin (2), non-cognate substrates also undergo a Pictet-Spengler reaction (PSR) catalyzed by strictosidine synthases (STR) with differing catalytic properties. We characterized the bisubstrate binding aspect of catalysis - order, affinity, and cooperativity - with STR orthologs from Rauvolfia serpentina (RsSTR) and Ophiorrhiza pumila (OpSTR) by an isothermal titration calorimetry (ITC) based 'proxy approach' that employed a non-reactive tryptamine analog (m1) to capture its inert ternary complexes with STRs and (2). ITC studies with OpSTR and (2) revealed 'tryptamine-first' cooperative binding with (1) and a simultaneous cooperative binding with (m1). Binding cooperativity among (m1) and (2) towards OpSTR was higher than RsSTR. Crystallographic study of RsSTR-(m1) complex helped to understand the unreactive binding of (m1) in terms of orientation and interactions in the RsSTR pocket. PSR with (m1) was revealed to be energetically unfeasible by the density functional theory (DFT) scans of the first hydrogen abstraction by RsSTR. The effect of pH on the bisubstrate binding to OpSTR was deciphered by molecular dynamics simulations (MDS), which also provided a molecular basis for the stability of complex of OpSTR with (m1) and (2). Therefore, we investigated STRs from a substrate binding perspective to inform drug-design and rational enzyme engineering efforts.
Assuntos
Rauwolfia , Alcaloides de Vinca , Alcaloides de Vinca/química , Alcaloides de Vinca/metabolismo , Rauwolfia/metabolismo , Catálise , TriptaminasRESUMO
Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18ß-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), Nb -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-ß-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-ß-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-ß-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56â µM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66â µM. The other isolates were inactive with IC50 values over 100â µM.
Assuntos
Alcaloides , Anisóis , Lignanas , Naftalenos , Rauwolfia , Animais , Camundongos , Lignanas/química , Células RAW 264.7 , Lipopolissacarídeos/farmacologia , Óxido Nítrico , Alcaloides/análise , Espectroscopia de Ressonância Magnética , Componentes Aéreos da Planta/química , Ioimbina , Estrutura MolecularRESUMO
The application of green synthesized nanocomposites for the prevention of environmental pollution is increasing nowadays. Here, a green composite has been synthesized by embedding MnO2 on Rauvolfia tetraphylla leaves using its leaf extract hereinafter termed as MnO2@RTL, and demonstrated for crystal violet (CV) dye removal from simulated and real wastewater. The surface properties of the material were determined by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), and Brunauer-Emmet-Teller (BET) surface area, pHZPC, and zeta potential. The material exhibits a remarkable adsorption capacity of 61.162 mg/g at 328 K and pH 7. The adsorption was best fitted with Pseudo-second-order kinetic (R2 = 0.998) and a combination of Langmuir and Freundlich isotherm model (R2 = 0.994-0.999). The thermodynamic study revealed spontaneous (ΔG values = - 2.988 to - 4.978 kJ/mol) and endothermic (ΔH values = 6.830 to 11.018 kJ/mol) adsorption. After adsorption, 80% regeneration occurred with 50% methanol, and recycled up to five times. Advantageously, the material was able to remove CV dye in the presence of coexistent ions and from industrial wastewater, confirming field applicability. The adsorption capacity of the material is superior to previously reported materials. The standard deviation and relative standard deviations have been evaluated to be 0.000422-0.000667 and 0.473-0.749%, which suggests the reliability of the experiments. The exhausted material, after recycling, was pyrolyzed to overcome the disposal problem. It was established as a secondary adsorbent with 73% efficiency which makes the material win-win. The material showed antibacterial properties with Staphylococcus aureus bacteria with a zone of inhibition 5 mm.
Assuntos
Rauwolfia , Poluentes Químicos da Água , Águas Residuárias , Violeta Genciana , Antibacterianos/farmacologia , Compostos de Manganês , Reprodutibilidade dos Testes , Óxidos , Termodinâmica , Adsorção , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: To investigate the effects of different concentrations of Rauwolfia extract (RE) on the proliferation of prostate cells in the rat model of benign prostatic hyperplasia (BPH). METHODS: We randomly divided 48 male SD rats into six groups of an equal number, BPH model control, finasteride, low-concentration RE, medium-concentration RE, high-concentration RE and normal control, and established a BPH model in the former five groups by subcutaneous injection of testosterone propionate following castration. We treated the rats of the finasteride and RE groups intragastrically with finasteride solution at 5 mg/kg and RE at 5, 10 and 20 mg/kg respectively, and those of the model control and normal control groups with an equal dose of normal saline, all once a day for 28 consecutive days. Then, we killed all the animals, collected their prostate tissue, obtained the wet weight and volume of the prostate, the prostate index and the contents of serum T and dihydrotestosterone (DHT), observed the morphological changes of the prostate tissue by HE staining, counted the glands in the prostate tissue, measured the intraglandular area, and determined the expressions of PCNA and α-SMA by immunohistochemistry. RESULTS: Compared with the rats of the normal control group, the BPH model controls showed significantly increased wet weight (ï¼»0.923 ± 0.15ï¼½ vs ï¼»1.455 ± 0.52ï¼½ g, P < 0.05), volume (ï¼»1.035 ± 0.29ï¼½ vs ï¼»1.687 ± 0.31ï¼½ ml, P < 0.05) and index of the prostate (ï¼»0.23 ± 0.04ï¼½% vs ï¼»0.37 ± 0.15ï¼½%, P < 0.05), dilation, hyperemia and edema of the prostatic stroma and vessels, and proliferation rate of the prostatic cells, but remarkably decreased number of glands (ï¼»20.35 ± 3.83ï¼½ vs ï¼»12.56 ± 2.58ï¼½, P < 0.05), epithelial thickness (ï¼»39.76 ± 5.20ï¼½ vs ï¼»19.52 ± 1.52ï¼½ µm, P < 0.05) and intraglandular area (ï¼»12.3 ± 1.21ï¼½ vs ï¼»5.96 ± 0.34ï¼½ ×103µm2, P < 0.05). In comparison with the BPH model controls, the animals treated with RE, especially in the high-concentration RE group, exhibited marked decreases in the weight (ï¼»1.455 ± 0.52ï¼½ vs ï¼»0.862 ± 0.31ï¼½ g, P < 0.05), volume ( ï¼»1.687 ± 0.31ï¼½ vs ï¼»0.952 ± 0.28ï¼½ ml, P < 0.05) and index of the prostate (ï¼»0.37 ± 0.15ï¼½% vs ï¼»0.22 ± 0.07ï¼½%, P < 0.05), dramatic improvement in the number of glands (ï¼»12.56 ± 2.58ï¼½ vs ï¼»18.36 ± 1.25ï¼½, P < 0.05), epithelial thickness (ï¼»39.76 ± 5.20ï¼½ vs ï¼»19.04 ± 3.89ï¼½ µm, P < 0.05) and intraglandular area (ï¼»5.96 ± 0.34ï¼½ vs ï¼»10.25 ± 0.98ï¼½ ×103µm2, P<0.05ï¼½, P < 0.05), remarkable down-regulation of the expressions of PCNA and α-SMA, and significant reduction of the contents of serum T (ï¼»19.147 ± 3.214ï¼½ vs ï¼»6.016 ± 1.978ï¼½ ng/ml, P < 0.05) and DHT (ï¼»9.052 ± 0.633ï¼½ vs ï¼»2.532 ± 0.386ï¼½ ng/ml, P < 0.05). CONCLUSION: Rauwolfia extract can inhibit the proliferation of prostate cells and relieve BPH symptoms in a concentration-dependent manner in rats with BPH.
Assuntos
Alcaloides , Hiperplasia Prostática , Rauwolfia , Humanos , Ratos , Masculino , Animais , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Finasterida/farmacologia , Rauwolfia/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley , Alcaloides/uso terapêutico , Di-Hidrotestosterona , Proliferação de Células , TestosteronaRESUMO
Rauwolfia vomitoria Afzel. is an antipsychotic plant used by several African communities in the management of psychiatric conditions with good outcomes. Concerns about its dosages on brain activity lead to this investigation of its action on the hippocampal microstructure.Twenty-four adult male Wistar rats of average weight 200 g, were assigned into four groups (n = 6): control; 200, 300 and 400 mg/kg body weight of RVroot bark extract, respectively. The administration was once daily, and orally for seven days. Daily observation of the animals was done till on day eight when they were sacrificed after deep anaesthesia. Each brain was processed for histology and immunohistochemical studies. Animals in the 200, 300 and 400 mg/kg RV groups appeared generally dull and drowsy, and barely fed. Their hippocampal histology showed neuronal atrophy and karyorrhexis, with no difference in cell count, although the pyramidal cell numbers decreased in the 300 and 400 mg/kg RV groups. Neuron-specific enolase decreased in the 400 mg/kg RV group, while neurofilament decreased in all test groups. Glial fibrillary acidic protein expression and density increased in the 200 and 300 mg/kg RV groups, but not the 400 mg/kg RV group, all compared with the control group.The given doses of RV root bark extractin adult Wistar rats showed sedative activities with hippocampal histopathological changes, which may not be reversible, thereby leading to the hippocampal functional deficit.
Introducción: Rauwolfia vomitoria (RV) Afzel es una planta antipsicótica utilizada por varias comunidades africanas en el tratamiento de enfermedades psiquiátricas con buenos resultados. Las preocupaciones sobre sus efecto sobre la actividad cerebral conducen a esta investigación de su acción sobre la microestructura del hipocampo.Materiales y métodos: Se asignaron veinticuatro ratas Wistar macho adultas de un peso medio de 200 g, en cuatro grupos (n = 6): control; 200, 300 y 400 mg / kg de peso corporal de extracto de corteza de raíz de RV, respectivamente. La administración fue una vez al día y por vía oral durante siete días. Se realizó una observación diaria de los animales hasta el día ocho, cuando fueron sacrificados después de una anestesia profunda. Cada cerebro fue procesado para estudios histológicos e inmunohistoquímicos.Resultados: Los animales en los grupos de RV de 200, 300 y 400 mg / kg parecían generalmente apagados y somnolientos, y apenas alimentados. Su histología hipocampal mostró atrofia neuronal y cariorrexis, sin diferencia en el recuento celular, aunque el número de células piramidales disminuyó en los grupos de RV de 300 y 400 mg / kg. La enolasa específica de neuronas disminuyó en el grupo de RV de 400 mg / kg, mientras que el neurofilamento disminuyó en todos los grupos de prueba. La expresión y densidad de la proteína fibrilar ácida glial aumentó en los grupos de RV de 200 y 300 mg / kg, pero no en el grupo de RV de 400 mg / kg, todos en comparación con el grupo de control.Conclusión: Las dosis administradas de extracto de corteza de raíz de RV en ratas Wistar adultas mostraron actividades sedantes, con cambios histopatológicos del hipocampo, que pueden no ser reversibles, lo que conduce al déficit funcional del hipocampo.
Assuntos
Animais , Ratos , Rauwolfia/química , Extratos Vegetais/uso terapêutico , Hipocampo/anatomia & histologia , Ratos WistarRESUMO
Rauwolfia vomitoria (RV) has potent sedative effect, which may result in severe unpleasant consequences if not controlled. This necessitated this study on the effect of Gongronema latifolium (GL) on RV-induced behaviour, biochemical activities, and histomorphology of the cerebral cortex. Eighteen male Wistar rats of average weight 266 g were grouped into three (13). Group 1 was the control administered 0.5 mL of Tween®20, while groups 2 and 3 were administered 150 mg/kg of RV, and a combination of 150 mg/kg of RV and 200 mg/kg of GL (RV+GL), respectively for seven days. Twelve hours after treatments, open field neurobehavioral test was carried-out and the animals euthanized. Their sera were analyzed, and their cerebral cortices routinely processed by H&E method. There was lower (p<0.05) ambulatory, rearing and freezing activities in the RV group, while there was no difference in aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities, as well as serum cholesterol and triglycerides levels in all the groups. Cerebral cortical neurohistology of RV and RV+GL groups showed most neurons appearing hypertrophied with pyknotic nuclei in some, and less cellular population compared with the control group. RV produces sedative behaviour, and cerebral cortical neurohistological changes, which GL combination may help modulate.
Rauwolfia vomitoria (RV) tiene un efecto sedante potente, el que puede provocar graves consecuencias si no es controlado. Se estudió el efecto de Gongronema latifolium (GL) sobre el comportamiento inducido por RV, como también en las actividades bioquímicas, e histomorfología de la corteza cerebral. Dieciocho ratas macho Wistar con un peso promedio de 266 g, fueron separadas en tres Grupos (13). El Grupo 1 (control) recibió 0,5 mL de Tween® 20, mientras que a los Grupos 2 y 3 se les administró, durante siete días, 150 mg/kg de RV y una combinación de 150 mg/kg de RV y 200 mg/kg de GL (RV + GL), respectivamente. Doce horas después de los tratamientos y pruebas neuroconductuales de campo abierto, los animales fueron sacrificados. Se analizaron los sueros y cortezas cerebrales, los cuales fueron procesados y teñidos on HE. Se observó menor actividad ambulatoria y de congelación (p<0,05) en el grupo RV, mientras que no hubo diferencia en la actividad aspartato aminotransferasa sérica y de fosfatasa alcalina, así como tampoco en los niveles de colesterol y triglicéridos séricos en todos los grupos. La neurohistología cortical cerebral de los grupos RV y RV + GL mostró que la mayoría de las neuronas aparecen hipertrofiadas con núcleos picnóticos, y una menor cantidad celular en comparación con el grupo control. La RV produce un comportamiento sedante, y cambios neurohistológicos a nivel de la corteza cerebral lo que podría ser modulado al combinarse con GL.
Assuntos
Animais , Masculino , Ratos , Apocynaceae , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos Wistar , RauwolfiaRESUMO
Staphylococci bacteria are involved in many human and animal infections and development of alternative antimicrobial drugs against pathogenic bacteria is of great interest to the pharmaceutical industry. This study investigated the in vitro effect of Rauvolfia grandiflora methanol extract (root bark fraction) (RGE) on the density of ATCC strains of Staphylococcus aureus and Staphylococcus epidermidis, and a clinical enterotoxin-producer, S. aureus bovine strain. The alkaloid, isoreserpiline, obtained from dichloromethane extract of R. grandiflora was ineffective against the strains tested. After incubation of staphylococci strains in the presence of 1.2 mg.mL-1 RGE, a significant inhibition of cell growth was observed using both spectrophotometry and ELISA assays. Twelve drugs were evaluated for their antimicrobial effects on culture RGE-treated cells using the disk diffusion method. Penicillin resistant strains became sensitive to the drug after RGE treatment. Furthermore, enterotoxin production by RGE-treated S. aureus was evaluated using a standardized ELISA method. Although staphylococcal LSA 88 bovine strain cells remained viable after exposure to the extract, enterotoxin production was precluded in 20 percent after RGE treatment. Significant interference in staphylococci cell density, drug sensitivity and enterotoxin secretion was observed after treatment. The study highlights the necessity to find new methods of disease prevention and new antibiotic therapies against staphylococcal infections.
Assuntos
Antibacterianos , Resistência a Medicamentos , Enterotoxinas/análise , Técnicas In Vitro , Rauwolfia/toxicidade , Infecções Estafilocócicas , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Ensaio de Imunoadsorção Enzimática , Métodos , MétodosRESUMO
INTRODUCTION: the search for new drugs with safer therapeutic profiles in Cardiology is still a need and natural products, particularly from plants, constitute an excellent source of new compounds. OBJECTIVE: to study the cardiac cellular actions of quebrachidine an indole alkaloid, extracted from the roots of Rauwolfia viridis R et S, known as Quebrachidine, which is structurally related to the antiarrhythmics ajmaline and prajmaline. METHODS: several complementary experimental approaches to evaluate the effects of quebrachidine on the electrophysiological and contractile properties of cardiac tissues and cells were used. RESULTS: quebrachidine increased the ventricular fibrillation threshold in anaesthetized rabbits. It decreased the maximum rate of depolarization and increased the duration of the ventricular action potential in different species. These actions were accompanied by a positive inotropic effect over a broad concentration range and were consistent with the increase in Ca2+ currents recorded in single ventricular cardiomyocytes. CONCLUSIONS: the present results demonstrate that quebrachidine keeps the antiarrhythmic profile of ajmaline and prajmaline but also demonstrates a net positive inotropic action on cardiac tissues predictive of better therapeutic safety margin. Our results suggest that ajmalan-like molecular structures could provide a sound basis for the search of effective antiarrhythmics with positive inotropic effect
INTRODUCCIÓN: la búsqueda de nuevos fármacos con perfiles terapéuticos más seguros en cardiología, es aun una necesidad y los productos naturales, particularmente de plantas, constituyen una fuente excelente de nuevos compuestos. OBJETIVOS: estudiar las acciones celulares cardíacas de la quebrachidina, un alcaloide indólico extraído de las raíces de Rauwolfia viridis R et S, el cual está estructuralmente relacionado con los antiarrítmicos ajmalina y prajmalina. MÉTODOS: se utilizaron diferentes modelos experimentales complementarios para evaluar los efectos de la quebrachidina sobre las propiedades electrofisiológicas y contráctiles de tejidos y células cardíacas. RESULTADOS: la quebrachidina incrementó el umbral para la fibrilación ventricular en conejos anestesiados. Este alcaloide redujo la velocidad máxima de despolarización y aumentó la duración del potencial de acción ventricular de diferentes especies. Estas acciones estuvieron acompañadas de un efecto inotrópico positivo en un amplio rango de concentraciones y asociadas a un incremento en las corrientes de Ca2+ en cardiomiocitos ventriculares aislados. CONCLUSIONES: estos resultados demuestran que la quebrachidina conserva el perfil antiarrítmico de la ajmalina y la prajmalina pero muestra un efecto inotrópico positivo neto en tejidos cardíacos lo cual predice un mejor margen de seguridad terapéutico. Los resultados sugieren que las estructuras moleculares con núcleo ajmalano pueden constituir una base firme para la búsqueda de antiarrítmicos con efecto inotrópico positivo
Assuntos
Alcaloides/isolamento & purificação , Traumatismos Cardíacos , RauwolfiaRESUMO
Rauvolfia ligustrina Roem et. Schult (Apocynaceae), commonly known as "paratudo" and "arrebenta-boi" is a small tree found in Brazilian Northeastern. Previous studies have demonstrated depressant and anticonvulsant properties of the ethanol extract of Rauvolfia ligustrina. The aim of the present study was the determination of the lethal dose 50 percent (LD50) and the effects of total alkaloid fraction (TAF) of the aerial parts of R. ligustrina in animal models of convulsion. It was found that the acute toxicity of TAF was 127.8 (112.5-145.2) mg/kg (i.p.) in mice. TAF (20 mg/kg, ip) significantly increased (p < 0.05) the latencies of clonic seizures induced by pentylenetetrazol (PTZ) and picrotoxin (PIC). However, TAF did not protect the animals in maximal electroshock (MES) induced seizures. These results suggest that TAF of R. ligustrina possesses anticonvulsant properties.
Rauvolfia ligustrina Roem. et Schult. (Apocynaceae) é uma planta amplamente distribuída no Nordeste Brasileiro, rica em alcalóides indólicos, conhecida popularmente como "paratudo" e "arrebenta-boi". O presente estudo buscou avaliar a dose letal 50 por cento (DL50) da fração de alcalóides totais (FAT) das partes aéreas da R. ligustrina e a sua possível atividade anticonvulsivantes em roedores. A FAT apresentou uma DL50, via intraperitoneal (i.p.), de 127,8 (112,5-145,2) mg/kg e foi efetiva, na dose de 20 mg/kg (i.p.), em proteger os animais das convulsões induzidas pelo pentilenotetrazol (PTZ) e picrotoxina (PIC) aumentando significativamente (p < 0,05) a latência para o aparecimento das convulsões, sendo um indicativo de um efeito anticonvulsivante.
Assuntos
Animais , Ratos , Anticonvulsivantes , Eletrochoque , Dose Letal Mediana , Pentilenotetrazol , Picrotoxina , RauwolfiaRESUMO
Se realizó un estudio químico de la raíz de la especie Rauvolfia viridis Roem. et Schult que crece en Cuba, con el objetivo de profundizar en este tema. Se aislaron, purificaron y caracterizaron diferentes alcaloides correspondientes a las bases débiles, entre los que se encuentran la ajmalidina, la -yohimbina, la quebrachidina, la reserpinina y la yohimbina. Se descarta la presencia de reserpina
Assuntos
Alcaloides de Triptamina e Secologanina/isolamento & purificação , Raízes de Plantas/química , RauwolfiaRESUMO
Se realizó un estudio químico de la raíz de la especie de Rauvolfia viridis Roem. et Schult que crece en Cuba, con el objetivo de profundizar en este tema. Se ailaron, purificaron y caracterizaron diferentes alcaloides correspondientes a las bases débiles, entre los que se encuentran la ajmalidina, la Alfa-yohimbina, la quebrachidina, la reserpina y la yohimbina. Se descarta la presencia de reserpina
Assuntos
Raízes de Plantas , Rauwolfia , Alcaloides de Triptamina e SecologaninaRESUMO
Se realizaron estudios farmacológicos preliminares de las decocciones y los extractos de raíces de dos especies de Rauwolfia salicifolia y la Rauwolfia caffra Sond, comparando sus efectos hipotensores con el de la Rauwolfia serpentina empleada en la clínica por su contenido en reserpina. Se muestra el efecto de estas Rauwolfias sobre el aparato cardiovascular, mediante el empleo de diversas técnicas, y se observa un efecto hipotensor en los alcaloides totales de raíces de Rauwolfia caffra Sond y en las decocciones de la Rauwolfia salicifolia
Assuntos
Cobaias , Ratos , Animais , Masculino , Feminino , Rauwolfia , Alcaloides de Triptamina e Secologanina/farmacologia , Hipertensão/induzido quimicamente , TiraminaRESUMO
Se dan los resultados del estudio farmacognóstico de las raíces de 3 especies exóticas de Rauwolfia: R. caffra Sond, R. serpentina (L) Benth. ex Kurz y R. vomitoria Afzel, recientemente introducidas en Cuba con vistas a su posible utilización como fuente de reserpina