Abstract
Several species of the genus Ocotea are used in traditional medicine due to their anti-inflammatory and analgesic properties. In this work we sought to investigate the effects of biseugenol, the main component of the hexane extract from the leaves of Ocotea cymbarum (Lauraceae), during a chronic inflammatory process induced by polyester-polyurethane sponge in mice. In addition to the inflammatory component, sponge discs also allowed us to evaluate parameters associated with the formation of new blood vessels and the deposition and organization of the extracellular matrix, processes that are related to the chronification of the inflammatory response. Daily treatment with biseugenol (0.1, 1 or 10 µg in 10 µl of 0.5% DMSO) inhibited the synthesis of inflammatory cytokines (TNF-α, CXCL-1 and CCL2) and the neutrophil and macrophage infiltrate into to the implants, indirectly evaluated by the activity of myeloperoxidase and N-acetyl-β-d-glycosaminidase enzymes, respectively. In implants treated with biseugenol, we observed a reduction in angiogenesis, assessed through histological quantification of mean number of blood vessels, the levels of the pro-angiogenic cytokines FGF and VEGF and the activity of metalloproteinases. Except for VEGF levels, all mentioned parameters showed significant reductions after treatment with biseugenol. Finally, the administration of the compound also reduced TGF-β1 levels, collagen synthesis and deposition, in addition to modifying the organization of the newly formed matrix, presenting a potential anti-fibrotic effect. Therefore, our results demonstrate the potential therapeutic use of biseugenol for the treatment of a series of pathological conditions, where parameters associated with inflammation, angiogenesis and fibrogenesis are deregulated.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
Authors thank the Rede de Biotérios de Roedores from the Federal University of Uberlândia (REBIR/UFU).
Funding
This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (446480/2014-2; 301354-2019-7 and 150814/2021-6), Fundação de Amparo à Pesquisa de Minas Gerais—FAPEMIG (APQ-04436-10 and APQ-02238-14), Instituto Nacional de Ciência e Tecnologia—INCT/NanoBiofar, Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (2021/02789-7), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (financial code 001).
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BAF: Conceptualization, methodology, formal analysis, investigation, writing-original draft preparation. FBRM: Methodology, formal analysis, investigation. KSG: Methodology, formal analysis, investigation. DCSS: Methodology, formal analysis, investigation. JHGL: Conceptualization, supervision, writing—review & editing, funding acquisition, project administration. FAA: Conceptualization, supervision, writing—review & editing, funding acquisition, project administration.
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Ferreira, B.A., de Moura, F.B.R., Gomes, K.S. et al. Biseugenol from Ocotea cymbarum (Lauraceae) attenuates inflammation, angiogenesis and collagen deposition of sponge-induced fibrovascular tissue in mice. Inflammopharmacol 31, 1539–1549 (2023). https://doi.org/10.1007/s10787-023-01210-3
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DOI: https://doi.org/10.1007/s10787-023-01210-3