Activity of physalin F in a collagen-induced arthritis model.
The effects of physalin F (1), a steroid derivative purified from Physalis angulata, were investigated in models of collagen-induced arthritis in DBA/1 mice and allergic airway inflammation in BALB/c mice. Oral treatment with 1 or dexamethasone caused a marked decrease in paw edema and joint inflammation when compared to vehicle-treated arthritic mice. In contrast, treatment with 1 had no effect in mice with allergic airway inflammation caused by ovalbumin immunization, whereas dexamethasone significantly reduced the number of inflammatory cells and eosinophils in the broncoalveolar lavage fluid and in lung sections of challenged mice. To further demonstrate that 1 acts through a mechanism different from that of glucocorticoids, a nuclear translocation assay was performed of the glucocorticoid receptor (GR) using COS-7 cells transfected with a plasmid encoding for a yellow fluorescent protein (YFP)-GR fusion protein. Untreated or treated cells with 1 had YFP staining mainly in the cytoplasm, whereas in dexamethasone-treated cells the YFP staining was concentrated in the nuclei. It is concluded that the mechanism of the immunosuppressive activity of physalin F is distinct from that of the glucocorticoids.
Brustolim
Daniele
D
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
Vasconcelos
Juliana F
JF
Freitas
Luiz Antônio R
LA
Teixeira
Mauro M
MM
Farias
Marcel T
MT
Ribeiro
Yvone M
YM
Tomassini
Therezinha C B
TC
Oliveira
Geraldo G S
GG
Pontes-de-Carvalho
Lain C
LC
Ribeiro-dos-Santos
Ricardo
R
Soares
Milena B P
MB
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental; D019556:COS Cells; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010047:Ovalbumin / Q000008:administration & dosage; D032321:Physalis / Q000737:chemistry; D012632:Secosteroids / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012632:Secosteroids; C075425:physalin F; D003907:Dexamethasone; D010047:Ovalbumin