Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steroids purified from Physalis angulata L.
Physalis angulata L. is an annual herb widely used in popular medicine for the treatment of a variety of pathologies. Here, we tested immunomodulatory activities of physalins, seco-steroids purified from P. angulata extracts. Addition of physalins B, F or G, but not D, caused a reduction in nitric oxide production by macrophages stimulated with lipopolysaccaride and interferon-gamma. In the presence of physalin B, macrophages stimulated with lipopolysaccaride, alone or in combination with interferon-gamma, produced lower levels of tumour necrosis factor (TNF)-alpha, interleukin-6 and interleukin-12. The inhibitory activity of physalin B, unlike that of dexamethasone, was not reversed by RU486 [(4-dimethylamino) phenyl-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], an antiglucocorticoid. Physalin B-treated mice had lower levels of serum TNF-alpha than control mice after lipopolysaccaride challenge. More importantly, mice injected with physalins B, F or G survived after a lethal lipopolysaccaride challenge. These results demonstrate that seco-steroids from P. angulata are potent immunomodulatory substances and act through a mechanism distinct from that of dexamethasone.
Soares
Milena B P
MB
Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121-Brotas-FIOCRUZ, 40295-001 BA, Salvador, Brazil. milena@cpqgm@fiocruz.br
Bellintani
Moema C
MC
Ribeiro
Ivone M
IM
Tomassini
Therezinha C B
TC
Ribeiro dos Santos
Ricardo
R
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D032321:Physalis / Q000737:chemistry*; D010840:Phytosterols / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012632:Secosteroids; D013256:Steroids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D006727:Hormone Antagonists; D007783:Lactones; D008070:Lipopolysaccharides; D010840:Phytosterols; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D012632:Secosteroids; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C441429:physalin D; C033270:physalin B; D009569:Nitric Oxide; D015735:Mifepristone; C075425:physalin F