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


OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Daniel Augusto Gasparin Bueno
DA
Mendes
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Bruna da Silva
BD
Soley
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Arthur da Silveira
AD
Prudente
Department of Pharmacy, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Graziela
G
Sponchiado
Department of Botany, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Bárbara Guerreira Alpande
BG
Ferreira
Center for Chemical-Pharmaceutical Research, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
Matheus Corrêa
MC
Dos Santos
Center for Chemical-Pharmaceutical Research, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
Amanda Sobreiro Modesto
AS
de Andrade
Center for Chemical-Pharmaceutical Research, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
Clarissa de Medeiros
CM
Amorim
Center for Chemical-Pharmaceutical Research, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
Tania Mari Bellé
TM
Bresolin
Center for Chemical-Pharmaceutical Research, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
Christiane
C
Meyre-Silva
Department of Botany, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Katia Christina
KC
Zuffellato-Ribas
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Jamil
J
Assreuy
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Michel Fleith
MF
Otuki
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: cabrini@ufpr.br.
Daniela de Almeida
DA
Cabrini
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001938:Brazil; D002351:Carrageenan / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D031287:Sapium / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D002351:Carrageenan; D013755:Tetradecanoylphorbol Acetate
Glucocorticoids; Medicinal plants; Sapium glandulatum; Skin; Skin inflammation