Abstract
Chalcones present potential therapeutic activities reported on literature, which led us to evaluate the anti-inflammatory effects and the acute toxicity of 2′,6′-dihydroxy-4′-methoxydihydrochalcone (DHMDC) using in vitro and in vivo models. The anti-inflammatory activity was firstly in vitro investigated using macrophages (RAW 264.7) and neutrophils previously treated with DHMCD activated with lipopolysaccharide (LPS). Nitrite, IL-1β, and TNF levels were measured in the macrophage culture supernatant, and the adhesion molecule expression (CD62L, CD49D, and CD18) was evaluated in neutrophils. Then, carrageenan-induced inflammation was performed in the subcutaneous tissue of male Swiss mice. Leukocyte migration and histological analysis were performed in the pouches. Toxicological studies were carried out on female Swiss mice (600 mg/kg) through biochemical parameters and histopathological analysis. In vitro, the DHMCD significantly reduced the IL-1β, TNF, and nitrite levels. The DHMCD was also able to modulate the percentage of positive neutrophils for CD62L, without modifying the expression of CD18 or CD49d. In vivo, DHMCD (3 mg/kg, p.o.) significantly reduced neutrophil migration to inflammatory exudate and subcutaneous tissue. No evidence of toxic effect was observed considering the biochemical parameters and histopathological analysis of liver and kidney. Together, the obtained data shows that DHMCD presents anti-inflammatory activity by modulating the macrophage inflammatory protein secretion and also by blocking the CD62L cleavage in neutrophils. Furthermore, there was not any evidence of toxic effect in acute toxicological analysis.
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Acknowledgments
This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 429505/2018-3), the Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES), and the Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), M.L.C., L.B., R.N., and S.R.S were post-graduate students in Pharmaceutical Science and are recipients of CAPES grants (Financial code 001) and L.L. was a graduate student in Pharmacy recipient of CNPq (PIBIC) grant (Financial code 001). N.L.M.Q. is a researcher granted by CNPq (305550/2018-7).
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J.R.S. and N.L.M.Q. conceived and designed the research. M.L.C., L.B., R.N., S.R.S., S.C.B., and L.C. conducted experiments. A.M. and M.M.S. contributed new reagents or analytical tools. J.R.S. and M.L.C. analyzed data. J.R.S., M.L.C., and N.L.M.Q. wrote the manuscript. All authors read and approved the manuscript and all data was generated in-house and that no paper mill was used.
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Cerutti, M.L., Benvenutti, L., Nunes, R. et al. Effects of 2′,6′-dihydroxy-4′-methoxydihidrochalcone on innate inflammatory response. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2061–2072 (2020). https://doi.org/10.1007/s00210-020-01922-1
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DOI: https://doi.org/10.1007/s00210-020-01922-1