Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models

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-β-D-glucosaminidase (NAG) activities and nitric oxide (NO) levels were determined, and histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-β-dehydrogenase, and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton-oil-, AA- and phenol-induced ear oedema (p < 0.001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and NO levels were decreased (p < 0.001). The histopathological data revealed that inflammatory parameters (oedema thickness, leukocyte 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.

Keywords: cyclooxygenase; inflammation; molecular docking; prostaglandin-E(2)-9-reductase; solidagenone.