RESUMEN
Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.
Asunto(s)
ATPasas Transportadoras de Calcio/metabolismo , Diterpenos de Tipo Kaurano/uso terapéutico , Diseño de Fármacos , Plasmodium falciparum/enzimología , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Wedelia/química , Antimaláricos/metabolismo , Artemisininas/metabolismo , Calcio/metabolismo , Diterpenos de Tipo Kaurano/síntesis química , Diterpenos de Tipo Kaurano/farmacología , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Tapsigargina/farmacología , Wedelia/clasificaciónRESUMEN
A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled.
Asunto(s)
Enfermedades de los Bovinos/etiología , Intoxicación por Plantas/veterinaria , Wedelia/envenenamiento , Alimentación Animal , Animales , Argentina/epidemiología , Enfermedades de los Conductos Biliares/etiología , Enfermedades de los Conductos Biliares/patología , Enfermedades de los Conductos Biliares/veterinaria , Bovinos , Enfermedades de los Bovinos/economía , Enfermedades de los Bovinos/patología , Brotes de Enfermedades/veterinaria , Diterpenos/envenenamiento , Edema/etiología , Edema/patología , Edema/veterinaria , Femenino , Enfermedades de la Vesícula Biliar/etiología , Enfermedades de la Vesícula Biliar/patología , Enfermedades de la Vesícula Biliar/veterinaria , Hemorragia/etiología , Hemorragia/patología , Hemorragia/veterinaria , Hígado/patología , Hepatopatías/etiología , Hepatopatías/patología , Hepatopatías/veterinaria , Masculino , Medicago sativa , Necrosis/veterinaria , Intoxicación por Plantas/mortalidad , Intoxicación por Plantas/patología , Plantas Tóxicas/química , Plantas Tóxicas/envenenamiento , Rumen/patología , Wedelia/químicaRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Uma recente reinvestigação das partes aéreas de Wedelia paludosa D.C. é descrita e relata, pela primeira vez, o isolamento do ácido iso-caurenóico desta espécie.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A new product of biotransformation of ent-16-oxo-17-norkauran-19-oic acid (1) by Fusarium proliferatum was isolated and identified as a 2beta-hydroxy derivative (2). The structure of 2 was elucidated on the basis of spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The allelopathic activity of compound 2 was evaluated on the growth of radicals and shoots of Lactuca sativa (lettuce). This is the first time that fungal hydroxylation at position C-2 has been reported on an ent-kaurane diterpene skeleton.
Asunto(s)
Diterpenos de Tipo Kaurano/química , Fusarium/metabolismo , Lactuca/efectos de los fármacos , Biotransformación , Brasil , Cristalografía por Rayos X , Hidroxilación , Lactuca/crecimiento & desarrollo , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Wedelia/químicaRESUMEN
Several in-vitro and in-vivo ethnopharmacological studies carried out with plants of the genus Wedelia have already demonstrated hepatoprotective effects in chemically-induced liver injury, including those induced by paracetamol. Here, the effects of the crude extract from Wedelia paludosa on paracetamol-induced hepatotoxicity in mice was investigated. Intraperitoneal injection of paracetamol (1,000 mg kg(-1)) caused 80% death after 24 h in mice, which was significantly reduced by oral pretreatment with W. paludosa (500 mg kg(-1)). Hepatotoxicity was observed 24 h after an intraperitoneal injection of paracetamol (600 mg kg(-1)), as evidenced by an increase in plasma activity of aspartate and alanine aminotransferases. That hepatotoxicity was significantly attenuated by W. paludosa pretreatment (100-500 mg kg(-1)) in a dose-response manner. Paracetamol (1,000 mg kg(-1)) drastically depleted total glutathione levels and decreased glutathione peroxidase and delta-aminolevulinate dehydratase activity in the liver, such effects not being prevented by pretreatment with W. paludosa. Neither paracetamol treatment alone nor pretreatment with W. paludosa altered glutathione reductase and glutathione S-transferase activity or the levels of end-products of lipid peroxidation. In conclusion, we found that W. paludosa protected against paracetamol-induced hepatotoxicity, an effect not observed over oxidative stress-related parameters. Hepatoprotection is likely mediated by some terpenes present in W. paludosa extract. However, further studies will be required to explain the mechanisms involved in the hepatoprotection afforded by W. paludosa.
Asunto(s)
Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Wedelia/química , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado/metabolismo , Hepatopatías/metabolismo , Masculino , Ratones , Estrés Oxidativo , Extractos Vegetales/farmacología , Pruebas de Toxicidad AgudaRESUMEN
We evaluated the variation of the concentration of kaurenoic acid (1), which is a bioactive diterpene, in leaves, flowers, stems and roots from Wedelia paludosa (Acmela brasiliensis) for different seasons using the HRGC/FID method. The results indicated that the concentration of 1 is higher in the roots and stems during the autumn. The pharmacological results suggested that kaurenoic acid is responsible, at least in part, for the hypoglycemic potential detected in this plant.
Asunto(s)
Glucemia/metabolismo , Diterpenos/análisis , Diterpenos/farmacología , Hipoglucemiantes/análisis , Hipoglucemiantes/farmacología , Extractos Vegetales/análisis , Wedelia/química , Animales , Glucemia/efectos de los fármacos , Diterpenos/metabolismo , Prueba de Tolerancia a la Glucosa , Gliburida/farmacología , Hiperglucemia/sangre , Masculino , Ratas , Ratas Wistar , Estaciones del AñoRESUMEN
Wedelia paludosa (Acmela brasiliensis) (Asteraceae), a traditionally used native Brazilian medicinal plant, showed antifungal activity against dermatophytes in dilution tests. The hexane, dichloromethane and butanol fractions displayed activity against Epidermophyton floccosum, Trichophyton rubrum and Trichophyton mentagrophytes, with minimal inhibitory concentrations between 250 and 1000 microg/mL. Two pure compounds, identified as kaurenoic acid (1) and luteolin (2), also showed activity against these dermatophytes.