Effects of Tithonia diversifolia (asteraceae) extract on innate inflammatory responses
2019
Abstract Ethnopharmacological relevance
Tithoniadiversifolia (Helms.) A. Gray, popularly known in Brazil as “margaridao” or “mao-de-Deus” has been used in the
folk medicineas anti-inflammatory and against other illnesses in several countries. Indeed, many studies show de effect of T. diversifolia in the inflammatory process, however, any of them have demonstrated the mechanism of cell migration. Aim of the study The aim of this investigation was to show the in vivo and in vitro effects of T. diversifolia leaves ethanol extract on neutrophil trafficking from the blood to the inflamed tissue and on cell-derived secretion of chemical mediators, as well as, the effects on inflammatory resolution and inflammatory pain. Materials and methods Anti-inflammatory activity was investigated using
carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally treated with the T. diversifolia extract (0.1, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and the secretion of chemical mediators (TNF, IL-6, IL-1β and
CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was performed. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced TNF, IL-6, IL-1β,
CXCL1and NO production, and adhesion molecule expression (CD62L and
CD18, flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 μg/mL). The resolution of inflammation was accessed by
efferocytosisassay, and the antinociceptive activity was investigated using
carrageenan-induced mechanical hypersensitivity. Results The oral treatment with T. diversifolia promoted reduction in the neutrophil migration as well as the decrease in total protein, TNF, IL-1β and
CXCL1levels in the inflamed exudate. In vitro treatment with T. diversifolia shedding of β2 integrin expressions, without alter CD62L expression. The extract was able to increase the
efferocytosisof apoptotic neutrophils, and the increase of the IL-10 and the decrease of TNF secretion. Additionally, the extract reduced the hypersensitivity induced by
carrageenan. Conclusions Together, the data herein obtained showed that T. diversifolia extract presented anti-inflammatory activity by inhibiting the cytokine and NO production, and also the leukocyte migration. The mechanisms involved in the extract anti-inflammatory effects include the impairment in the leukocyte migration to the inflamed tissue, the pro-resolution activity, and consequently the anti-hypersensitivity.
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