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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
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