Abstract
The tagitinins isolated of Tithonia diversifolia (Hemsl.) A. Gray, Asteraceae, are the most studied sesquiterpene lactones due to their wide spectrum of pharmacologic activities, especially related with nuclear factor-kappa B inhibition. Nevertheless, detailed studies about the mechanism of action of its active compounds are still lacking. Neutrophils perform a fundamental role in the inflammatory response to several etiologic factors. However, the effect of tagitinins on human neutrophil is not yet clearly known. We investigated the role of tagitinin C (1), tagitinin F (2) and tagitinin A (3) in activation and survival of human neutrophils to establish possible effects in their mechanisms of inflammation. Human neutrophils were purified from the peripheral blood and cultivated with tagitinins C (1), F (2) and A (3) in the presence or not of Escherichia coli lipopolysaccharide. The enzymatic activity, apoptosis and secretion of cytokines rate were determined after 18 h. Lipopolysaccharide-induced myeloperoxidase activity of human neutrophils was significantly inhibited only by tagitinin F (2). Apoptosis of neutrophils was increased in the presence of tagitinin C (1), and it occurred independently of the presence of lipopolysaccharide or dexamethasone. Tagitinins C (1), F (2) and A (3) decrease lipopolysaccharide-induced interleukin-6, interleukin-8 and Tumor necrosis factor alpha production by human neutrophils. Together, these results indicate that tagitinins exhibit anti-inflammatory action on human neutrophils. However, tagitinin F (2) was the only sesquiterpene lactone that decreased secretion of inflammatory products by neutrophils without inducing neutrophil apoptosis.
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Acknowledgments
The authors express their gratitude for CAPES, FAPESP and CNPq for funding, grants and scholarships. The authors were supported by FAPESP for grant #2008/57149-8 (scholarship to A.E.A. [2011/18174-0], T.M.D. [2010/19317-6], T.H.G. [2009/14127-7]), R.B.O. [2011/01862-0], D.A.C.P. [2008/02185-0 and 2010/10940-2], CAPES for scholarship to C.E.O. and B.A.R., and CNPq for scholarship to F.B.C. and A.P.C.
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APC, FBC, and THG conceived and designed the experiments; AEA, CEO, TMD, and THG for culture-related experiments; BAR, DACP, and RBO for purification and characterization of Tag; AEA, CEO, FBC, APC, and THG contributed to data analysis; APC and FBC contributed with reagents/materials/analysis tools and AEA, CEO, THG, DACP, BAR, RBO, FBC, and APC for paper writing. All authors have read the final manuscript and approved the submission.
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Abe, A.E., de Oliveira, C.E., Dalboni, T.M. et al. Anti-inflammatory sesquiterpene lactones from Tithonia diversifolia trigger different effects on human neutrophils. Rev. Bras. Farmacogn. 25, 111–116 (2015). https://doi.org/10.1016/j.bjp.2015.01.005
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DOI: https://doi.org/10.1016/j.bjp.2015.01.005