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New bicyclic [3.2.1] octane neolignans derivatives from Aniba firmula with potent in vivo anti-inflammatory activity on account of dual inhibition of PGE2 production and cell recruitment

Author:
Santos, Mario F.C., Alcântara, Bianca G.V., dos R. Feliciano, Cristiane, Silva, Aline F., Maiolini, Tatiane C.S., Neto, Albert K., Murgu, Michael, de Paula, Daniela A. Chagas, Soares, Marisi G.
Source:
Phytochemistry letters 2019 v.30 pp. 31-37
ISSN:
1874-3900
Subject:
Aniba, Croton, adverse effects, aerial parts, anti-inflammatory activity, anti-inflammatory agents, bioactive compounds, ears, edema, fractionation, high performance liquid chromatography, lignans, mechanism of action, mice, neutrophils, octane, spectral analysis
Abstract:
Two new bicyclic octane neolignans, 1, 2, and the known bicyclic octane neolignan 3 were obtained by HPLC fractionation of the crude extract of aerial parts and the stem of Aniba firmula (Lauraceae’s family). The identification of its structures was made by spectroscopic analysis. The Lauraceae is well-known for its anti-inflammatory potential and is a rich source of bioactive compounds. The eff ;ects of 1 and 2 on inflammation were evaluated in an in vivo assay in mice. It was found that 1 and 2 significantly inhibited croton oil-induced ear edema when compared with their respective reference drugs. Moreover, 1 also inhibited neutrophil recruitment in an MPO assay. The level of PGE2 was further evaluated and supported the hypothesis that edema was inhibited through the COX pathway. As long as the level of LTB4 of 1 was similar to that of the negative control, we assert that the LOX pathway was not inhibited for this compound. Thus, these findings demonstrate that 1 has anti-inflammatory activity by a mechanism of action different from the common anti-inflammatory drugs available. This may mean that different neolignan classes could be sources of lead compounds prior to the development of new anti-inflammatory drugs, aiding in the search for higher efficacy and leading to fewer potential side effects.
Agid:
6287341