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Basic Clin Pharmacol Toxicol ; 128(1): 91-102, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32780565

RESUMO

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.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Dermatite/prevenção & controle , Edema/prevenção & controle , Furanos/farmacologia , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Proteínas de Membrana/antagonistas & inibidores , Naftalenos/farmacologia , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Solidago , Acetilglucosaminidase/metabolismo , Animais , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Inibidores de Ciclo-Oxigenase/metabolismo , Dermatite/metabolismo , Dermatite/patologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Furanos/isolamento & purificação , Furanos/metabolismo , Ligação de Hidrogênio , Hidroxiprostaglandina Desidrogenases/metabolismo , Interleucina-6/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Naftalenos/isolamento & purificação , Naftalenos/metabolismo , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Ligação Proteica , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Solidago/química , Fator de Necrose Tumoral alfa/metabolismo
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