Effects of 2′,6′-dihydroxy-4′-methoxydihidrochalcone on innate inflammatory response

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 393; no. 11; pp. 2061 - 2072
• Main Authors: Cerutti, Murilo Luiz, Benvenutti, Larissa, Nunes, Roberta, da Silva, Silvia Ramos, Barauna, Sara Cristiane, de Souza, Márcia Maria, Malheiros, Ângela, Lacava, Letícia, Quintão, Nara Lins Meira, Santin, José Roberto
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2020; Springer Nature B.V
• Subjects: Acute toxicity; Anti-inflammatory agents; Biomedical and Life Sciences; Biomedicine; CD18 antigen; CD49d antigen; IL-1β; Inflammation; Kidneys; L-selectin; Leukocyte migration; Leukocytes (neutrophilic); Lipopolysaccharides; Macrophage inflammatory protein; Neurosciences; Neutrophils; Original Article; Pharmacology/Toxicology; Toxicity; Toxicity testing; Tumor necrosis factor; Adhesion molecules; Inflammation; Mice; Neutrophil; Macrophages; Chalcone
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-020-01922-1

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.