[Millerenolide induces suppressive activity on human peripheral blood mononuclear cells].
BACKGROUND
Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene lactones are the active constituents of several plants from the Asteraceae family.


OBJECTIVE
To assess the in vitro effect of a sesquiterpene lactone (millerenolide).


METHODS
The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically.


RESULTS
Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/M phases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 microg/ml.


CONCLUSIONS
Millerenolide could be considered as a potential therapeutic agent with immunosuppressive properties.
Dupuy L
Ornar A
OA
Escuela de Química, Universidad de Costa Rica, San José, Costa Rica.
Murillo
Renato
R
Bonilla V
José A
JA
D000704:Analysis of Variance; D019659:Asteraceae / Q000737:chemistry; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D007166:Immunosuppressive Agents; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C532684:millerenolide; D009569:Nitric Oxide