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

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 propertie...

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Published in:	Phytomedicine (Stuttgart) Vol. 23; no. 13; pp. 1610 - 1620
Main Authors:	Mendes, Daniel Augusto Gasparin Bueno, Soley, Bruna da Silva, Prudente, Arthur da Silveira, Sponchiado, Graziela, Ferreira, Bárbara Guerreira Alpande, dos Santos, Matheus Corrêa, de Andrade, Amanda Sobreiro Modesto, Amorim, Clarissa de Medeiros, Bresolin, Tania Mari Bellé, Meyre-Silva, Christiane, Zuffellato-Ribas, Katia Christina, Assreuy, Jamil, Otuki, Michel Fleith, Cabrini, Daniela de Almeida
Format:	Journal Article
Language:	English
Published:	Germany Elsevier GmbH 01-12-2016
Subjects:	Administration, Oral Administration, Topical Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Brazil Carrageenan - toxicity Cytokines - metabolism Drug Evaluation, Preclinical - methods Edema - chemically induced Edema - drug therapy Glucocorticoids Male Medicinal plants Mice Plant Extracts - administration & dosage Plant Extracts - pharmacology Plant Leaves - chemistry Plants, Medicinal - chemistry Receptors, Glucocorticoid - metabolism Sapium - chemistry Sapium glandulatum Skin Skin inflammation Tetradecanoylphorbol Acetate - toxicity Medicinal plants Skin inflammation IL Glucocorticoids TPA Sapium glandulatum ICAM-1 GR MPO PEG400 TNF-α NAG EHSG Skin
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Summary:	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. 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. 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. 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. 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. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0944-7113 1618-095X
DOI:	10.1016/j.phymed.2016.10.003