Vestitol Isolated from Brazilian Red Propolis Inhibits Neutrophils Migration in the Inflammatory Process: Elucidation of the Mechanism of Action

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 4; pp. 954 - 960
• Main Authors: Franchin, Marcelo, Cólon, David F, Castanheira, Fernanda V. S, da Cunha, Marcos G, Bueno-Silva, Bruno, Alencar, Severino M, Cunha, Thiago M, Rosalen, Pedro L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 22.04.2016
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Brazil; Chemokine CXCL1; Flavonoids - chemistry; Flavonoids - isolation & purification; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Neutrophil Infiltration; Neutrophils - drug effects; Nitric Oxide Synthase Type II - genetics; Propolis - chemistry; Brazil
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00938

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.