ABSTRACT
Isoflavonoids have been largely studied due to their distinct biological activities identified thus far. Herein, we evaluated the activity of neovestitol, an isoflavonoid isolated from Brazilian red propolis, in acute and chronic inflammation. As for acute inflammation, we found that neovestitol reduced neutrophil migration, leukocyte rolling and adhesion, as well as expression of ICAM-1 in the mesenteric microcirculation during lipopolysaccharide-induced acute peritonitis. No changes were observed in the levels of TNF-α, CXCL1/KC and CXCL2/MIP-2 upon pretreatment with neovestitol. The administration of an inducible nitric oxide synthase (iNOS) inhibitor abolished the inhibitory effects of neovestitol in neutrophil migration and ICAM-1 expression. Nitrite levels increased upon treatment with neovestitol. No effects of neovestitol were observed on the chemotaxis of neutrophils in vitro. As for chronic inflammation, neovestitol also reduced the clinical score and joint damage in a collagen-induced arthritis model. There was no change in the frequency of IL-17-producing TCD4+ cells. In addition, pretreatment with neovestitol reduced the levels of IL-6. These results demonstrate a potential anti-inflammatory activity of neovestitol, which may be useful for therapeutic purposes and/or as a nutraceutical.
Subject(s)
Arthritis, Experimental/prevention & control , Flavonoids/therapeutic use , Interleukin-6/metabolism , Nitric Oxide/metabolism , Peritonitis/prevention & control , Propolis/chemistry , Acute Disease , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/etiology , Brazil , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Chronic Disease , Cytokines/metabolism , Flavonoids/chemistry , Flavonoids/pharmacology , Guanidines/pharmacology , Lipopolysaccharides/toxicity , Mesenteric Veins/drug effects , Mesenteric Veins/metabolism , Mesenteric Veins/pathology , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/immunology , Peritonitis/etiology , Propolis/metabolismABSTRACT
Vestitol is an isoflavonoid isolated from Brazilian red propolis with potential anti-inflammatory activity. This study investigated the mechanism of action of vestitol on the modulation of neutrophil migration in the inflammatory process. Pre-treatment with vestitol at 1, 3, or 10 mg/kg reduced LPS- or mBSA-induced neutrophil migration and the release of CXCL1/KC and CXCL2/MIP-2 in vivo. Likewise, pre-treatment with vestitol at 1, 3, or 10 µM reduced the levels of CXCL1/KC and CXCL2/MIP-2 in macrophage supernatants in vitro. Moreover, the administration of vestitol (10 mg/kg) reduced leukocyte rolling and adherence in the mesenteric microcirculation of mice. The pre-treatment with vestitol (10 mg/kg) in iNOS(-/-) mice did not block its activity concerning neutrophil migration. With regard to the activity of vestitol on neutrophils isolated from the bone marrow of mice, there was a reduction on the chemotaxis of CXCL2/MIP-2 or LTB4-induced neutrophils and on calcium influx after pre-treatment with the compound at 3 or 10 µM. There was no change in CXCR2 expression by neutrophils treated with vestitol at 10 µM. These findings demonstrate that vestitol is a promising novel anti-inflammatory agent.
