In vitro activity of labdane diterpene from Alomia myriadenia (Asteraceae): immunosuppression via induction of apoptosis in monocytes.
A screening program in Brazilian flora was carried out to detect the presence of immunosuppressive compounds by using the in vitro phytohemagglutinin A (PHA)-induced human peripheral blood mononuclear cell (PBMC) proliferation assay. In this screening, we isolated from Alomia myriadenia Schultz-Bip. ex. Baker (Asteraceae), a labdane-type diterpene named myriadenolide. Incubation of human PBMC with this compound reduced significantly the percentage of CD14(+) cells, but it has no effect on the relative amount of CD3(+)CD4(-)CD8(+) and CD3(+)CD4(+)CD8(-) T lymphocyte subpopulations. Neither viability nor proliferative competence of T lymphocytes was significantly affected by myriadenolide. The toxic effect on monocytes (CD14(+) cells) may explain the inhibitory effect observed on PHA-induced lymphocyte proliferation. The cytotoxic effect of myriadenolide on monocytes was determined by measuring the percentage of hypodiploid nuclei content by propidium iodide staining, electron microscopy and simultaneous detection of CD14 and annexin V binding by flow cytometry. The results showed that myriadenolide induces a dose-dependent apoptosis in monocytes and thus explain the immunosuppressive effect observed.
Souza-Fagundes
Elaine M
EM
Laboratório de Química de Produtos Naturais, Centro de Pequisas René Rachou-Fiocruz, Av. Augusto de Lima 1715 Barro Preto, Belo Horizonte 30190-002, Brazil.
Gazzinelli
Giovanni
G
Parreira
Gleydes Gambogi
GG
Martins-Filho
Olindo A
OA
Amarante-Mendes
Gustavo P
GP
Corrêa-Oliveira
Rodrigo
R
Zani
Carlos L
CL
D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004247:DNA / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000378:metabolism; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects*
D017304:Annexin A5; D004224:Diterpenes; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; C433017:labdane; C479637:myriadenolide; D004247:DNA