Modulação dos parâmetros inflamatórios in vivo e in vitro por um inibidor de tripsina purificado de Libidibia ferrea (Mart. ex. Tul) L.P. Queiroz

Abstract

Libidibia ferrea is a native Brazilian tree with extensive popular use. Its leaves, bark, fruits seeds are used as anti-inflammatory and analgesic by riverside populations in the Brazilian North and Northeast regions. The trypsin inhibitor purified from its seeds (LfTI) has biological activities such as fungicide, antimicrobial and anticoagulant. Purified protease inhibitors from seeds of species from L. ferrea family (Fabaceae) have anti-inflammatory and immunoprotective action. Thus, this study aimed at evaluating the anti-inflammatory and anti-nociceptive response of LfTI in Swiss mice using in vitro assays, analyzing cellular viability, and macrophage H2O2 production and adhesion; and in vivo assays, analyzing leukocytes recruitment into the peritoneal cavity, nitric oxide (NO) production, vascular permeability, paw edema, abdominal writhing and formalin test. In vitro, LfTI (2, 50, 250 µg/mL) did not alter macrophage viability. Also, LfTI (2, 50, 250 µg/mL) inhibited (50 µg/mL) macrophages H2O2 production (48.4%) and adhesion (49.4%). In vivo, LfTI (0.6, 3 and 15 mg/Kg) decreased polymorphonuclear cell recruitment in a dose-dependent manner (50.5%, 77% and 94.5%). LfTI (3 mg/Kg) inhibited NO release (53%), vascular permeability (49.7%), and paw edema at different minutes. Still, LfTI inhibited paw licking time by 46.1% in the first phase of nociception (neurogenic pain), however, it did not inhibit this effect in the second phase (inflammatory pain) in the formalin test and it also did not inhibit the abdominal contortions induced by acetic acid. Our results for the first time show that LfTI has anti-inflammatory and neurogenic pain inhibitory effects.