Estudo do potencial anti-inflamatório de frações isoladas de Pterodon polygalaeflorus Benth.

Abstract

The species Pterodon polygalaeflorus Benth., commonly known as sucupira, belongs to the Fabaceae family. The Pterodon genus is known for having several species used in traditional medicine, mainly for the treatment of rheumatic diseases. Various studies report the biological activities in this genus and associate its effects with the presence of diterpenoid compounds with a vouacapane skeleton. This study aimed to investigate the anti-inflammatory effects of extracts and fractions obtained from P. polygalaeflorus fruits. To optimize diterpene extraction, three techniques were tested: maceration in methanol (EMPpg–35.5%), hydrodistillation followed by maceration of the residues in 100% methanol or ethanol (ErMPpg–52.6% and ErEPpg– 39.6%), and sequential extraction of the residues with 100% methanol (ErsMPpg–4.3%). Phytochemical analysis of the extracts revealed a high prevalence of vouacapane derivatives in the extracts obtained after hydrodistillation, making up 56-66% of the total compounds. Following biological activity screening, ErMPpg was selected for further study, as it significantly reduced (53%) the inflammatory phase in the formalin-induced inflammation model. ErMPpg also inhibited NO production (10.3-77.5%) without reducing mitochondrial reductive activity at most concentrations tested. In the air pouch model, ErMPpg (25 mg/kg) exhibited anti-inflammatory activity by reducing exudate volume (31.6%), protein concentration (83.7%), and leukocyte migration (49.9%), including polymorphonuclear cells (PMNs) (54.9%) and mononuclear cells (45.1%). In the pouch tissue, ErMPpg reduced macroscopic inflammatory parameters, leading to a thinner internal membrane and less cellular infiltration, along with tissue remodeling. In the thioglycolate-induced peritonitis model, ErMPpg (1-25 mg/kg) inhibited leukocyte migration to the peritoneal cavity (36.5-46.4%), particularly mononuclear cells (46-59.5%). Across all doses tested (0.32 – 25000 µg/kg), ErMPpg significantly reduced leukocyte migration (49.4-85.8%), reflected in a PMN reduction of 60.6-74.5%. For fractionation, liquid-liquid partitioning was used, where solvents of increasing polarity generated hexane (FrHex-46,8%), dichloromethane (FrDCM-30,2%), and ethyl acetate (FrEtOAc-6,6%) fractions, with the remaining material forming the hydroalcoholic residue (ResOH-4,8%). Fractionation efficiently produced fractions with high diterpene content, as confirmed by phytochemical analysis. The anti-inflammatory effects were assessed in the carrageenan-induced peritonitis model. Except for ResOH, all fractions (0.32 µg/kg) inhibited leukocyte migration (56.2-60.3%), reflected in a PMN reduction of 49.9-55%. Additionally, they modulated pro-inflammatory cytokine levels, especially FrHex, which inhibited TNF-α (69.3%) and IL-1β (67.8%) in the peritoneal exudate.