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Basic Clin Pharmacol Toxicol ; 128(1): 91-102, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32780565

ABSTRACT

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.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Dermatitis/prevention & control , Edema/prevention & control , Furans/pharmacology , Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors , Membrane Proteins/antagonists & inhibitors , Naphthalenes/pharmacology , Plant Extracts/pharmacology , Skin/drug effects , Solidago , Acetylglucosaminidase/metabolism , Animals , Cyclooxygenase 1/metabolism , Cyclooxygenase Inhibitors/isolation & purification , Cyclooxygenase Inhibitors/metabolism , Dermatitis/metabolism , Dermatitis/pathology , Disease Models, Animal , Edema/chemically induced , Edema/metabolism , Edema/pathology , Furans/isolation & purification , Furans/metabolism , Hydrogen Bonding , Hydroxyprostaglandin Dehydrogenases/metabolism , Interleukin-6/metabolism , Male , Membrane Proteins/metabolism , Mice , Molecular Docking Simulation , Naphthalenes/isolation & purification , Naphthalenes/metabolism , Nitric Oxide/metabolism , Peroxidase/metabolism , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Protein Binding , Signal Transduction , Skin/metabolism , Skin/pathology , Solidago/chemistry , Tumor Necrosis Factor-alpha/metabolism
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