Hydroalcoholic extract of Sapium glandulatum (Vell.) Pax displays potent anti-inflammatory activities through a glucocorticoid receptor-dependent pathway

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• 作者：Daniel Augusto Gasparin Bueno Mendes^a ; Bruna da Silva Soley^a ; Arthur da Silveira Prudente^a ; Graziela Sponchiado^b ; Bá ; rbara Guerreira Alpande Ferreira^c ; Matheus Corrê ; a dos Santos^d ; Amanda Sobreiro Modesto de Andrade^d ; Clarissa de Medeiros Amorim^d ; Tania Mari Bellé ; Bresolin^d ; Christiane Meyre-Silva^d ; Katia Christina Zuffellato-Ribas^c ; Jamil Assreuy^e ; Michel Fleith Otuki^a ; Daniela de Almeida Cabrini^a ; ^{cabrini@ufpr.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Sapium glandulatum ; Medicinal plants ; Skin ; Skin inflammation ; Glucocorticoids
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：23
• 期：13
• 页码：1610-1620
• 全文大小：3409 K

文摘

Ethnobotanical studies of the Sapium genus reveal that many species are widely used in several countries as therapeutic drugs and they are widely used in folk medicine for treatment of different diseases, including skin inflammation. This raises interest in the study of the pharmacological properties and phytochemical composition of these plants. The biological properties of Sapium glandulatum, a native species of southern Brazil, has not been reported in the literature.

Purpose

The aim of the present study was to investigate the anti-inflammatory action of the hydroalcoholic extract of Sapium glandulatum (EHSG) leaves in mouse models of acute or chronic skin inflammation.

Study design/methods

Topical effects of EHSG were evaluated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema in the ear. Systemic effects of the extract were studied in a TPA-induced ear edema model, as well as in a carrageenan-induced paw edema model. To gain insight into the mechanism by which EHSG blocked inflammation, we evaluated the role of glucocorticoid receptors (GR) using the TPA-induced ear edema model and also measured specific binding in a glucocorticoid assay. Possible adverse effects of EHSG were evaluated after multiple treatments with the extract in the skin atrophy model on the ear and with the alkaline comet assay.

Results

EHSG presented potent anti-inflammatory activity when applied topically in acute and chronic models, inhibiting edema formation and leukocyte migration as well as expression pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in the tissue. Similar anti-inflammatory effects were found following oral treatment in both ear and paw edema models. Strikingly, the EHSG-induced blockade of leukocyte migration was reversed by mifepristone, a GR antagonist. Additionally, a specific binding assay revealed that ESGH interacts with GR. Multiple treatments with EHSG failed to induce adverse effects when evaluated in the skin atrophy model and bone marrow genotoxicity test.

Conclusion

Taken together, our data suggest that EHSG is a potential source of anti-inflammatory tool compounds for the treatment of pro-inflammatory-derived skin diseases, and its mechanism of action may be, at least in part, via the GR pathway.