Anti-inflammatory sesquiterpene lactones from Tithonia diversifolia trigger different effects on human neutrophils

Abstract

a b s t r a c tThe 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.

Identification of tagitinin C from Tithonia diversifolia as antitrypanosomal compound using bioactivity-guided fractionation

“…Limited information is available related to ESI/MS behaviour of these sesquiterpenes. Abea et al (2015) reported proposed fragmentation pathways of tagitinin F. In our analysis, we observed that the tirotundin derivatives (compounds 4 and 5, Figure 3 presenting additional 14 Da due to the presence of a methyl group. Polyphenol derivatives, mainly caffeic acid derivatives and flavonoids, were also identified.…”

Anti-Inflammatory Activity of the Compositae Family and Its Therapeutic Potential

“…Tithonia diversifolia, native to the southeastern plains of Mexico and Central America but currently scattered throughout the world [109], is recognized worldwide for its antiparasitic, antimicrobial, and anti-inflammatory activities, among others. T. diversifolia, is a major source of bioactive molecules, among them phenolic compounds and terpenes (sesquiterpene lactones), such as tagitinin, which has been widely studied for its pharmacological properties, mainly related to the NF-κB factor [110], although its action mechanism is still unknown.…”

“…To evaluate the tagitinins and their effects related to inactivation and neutrophil survival plus establish the mechanisms of inflammation, Abe et al [110] investigated tagitinins A (13), C (14) and F (15) in purified and stimulated LPS neutrophils, where the enzymatic activity, apoptosis, and cytokinesterase secretion were determined after 18 h.…”

Ethnopharmacological Potential of Tithonia diversifolia (Hemsl) A. Gray

“…Recently, there has been a growing interest in sesquiterpene lactones isolated from T. diversifolia, with tagitinin C being one of the most interesting compounds. In general, tagitinin C has a wide range of pharmacological activities, including antiinflammatory and anticancer actions (Abe et al, 2015;Matheus Mendes et al, 2015).…”