In vitro activity of labdane diterpene from Alomia myriadenia (Asteraceae): immunosuppression via induction of apoptosis in monocytes

• Published in: International immunopharmacology Vol. 3; no. 3; pp. 383 - 392
• Main Authors: Souza-Fagundes, Elaine M, Gazzinelli, Giovanni, Parreira, Gleydes Gambogi, Martins-Filho, Olindo A, Amarante-Mendes, Gustavo P, Corrêa-Oliveira, Rodrigo, Zani, Carlos L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-03-2003; Elsevier
• Subjects: Alomia myriadenia; Annexin A5; Apoptosis; Apoptosis - drug effects; Asteraceae - chemistry; Biological and medical sciences; Cell Division - drug effects; Cell Survival - drug effects; Coculture Techniques; Diterpene labdane; Diterpenes - pharmacology; DNA - metabolism; Enzyme Inhibitors; Flow Cytometry; General pharmacology; Humans; Immunophenotyping; Immunosuppression; Immunosuppressive Agents - pharmacology; Lipopolysaccharide Receptors - biosynthesis; Lipopolysaccharide Receptors - metabolism; Medical sciences; Microscopy, Electron; Monocytes - drug effects; Natural products; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytohemagglutinin; South America; Brazil; America; Immunosuppression; Diterpene labdane; Phytohemagglutinin; Natural products; Alomia myriadenia; Apoptosis; Human; Cell culture; Terpenoid; Monocyte; Immunomodulation; Pharmacognosy; Extract; In vitro; Biological activity; Medicinal plant; Mononuclear cell; Cell death; Plant origin; Diterpene; Mechanism of action; Lymphocyte
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(02)00296-5

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.