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1.
Basic Clin Pharmacol Toxicol ; 128(1): 91-102, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32780565

RESUMEN

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-ß-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF-α, IL-6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX-1 and prostaglandin-E(2)-9-reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti-inflammatory agent.


Asunto(s)
Inhibidores de la Ciclooxigenasa/farmacología , Dermatitis/prevención & control , Edema/prevención & control , Furanos/farmacología , Hidroxiprostaglandina Deshidrogenasas/antagonistas & inhibidores , Proteínas de la Membrana/antagonistas & inhibidores , Naftalenos/farmacología , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Solidago , Acetilglucosaminidasa/metabolismo , Animales , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa/aislamiento & purificación , Inhibidores de la Ciclooxigenasa/metabolismo , Dermatitis/metabolismo , Dermatitis/patología , Modelos Animales de Enfermedad , Edema/inducido químicamente , Edema/metabolismo , Edema/patología , Furanos/aislamiento & purificación , Furanos/metabolismo , Enlace de Hidrógeno , Hidroxiprostaglandina Deshidrogenasas/metabolismo , Interleucina-6/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Naftalenos/aislamiento & purificación , Naftalenos/metabolismo , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Unión Proteica , Transducción de Señal , Piel/metabolismo , Piel/patología , Solidago/química , Factor de Necrosis Tumoral alfa/metabolismo
2.
BMJ Open ; 6(10): e011598, 2016 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-27797990

RESUMEN

PURPOSE: Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. PARTICIPANTS: Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. FINDINGS TO DATE: Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. FUTURE PLANS: A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Conjuntos de Datos como Asunto , Población Rural , Adulto , Antropometría , Brasil/epidemiología , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/psicología , Ritmo Circadiano , Estudios de Cohortes , Estudios Transversales , Etnicidad , Familia , Femenino , Estado de Salud , Humanos , Estilo de Vida , Masculino , Salud Mental , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Sueño , Medio Social , Encuestas y Cuestionarios
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