Trypsin inhibitor isolated from the seeds of Inga laurina (sw.) Willd decreased inflammatory and nociceptive responses in mice

Serine proteases (SP) are a defence mechanism for neutrophils, they induce recruitment and activation of immune cell, cytokine production and degradation of the extracellular matrix. However, the deregulated activity of SP or their inhibitors can lead to the development of inflammatory diseases. Natural inhibitors of serine proteases (iSP) from plants of the Fabaceae family have shown potential as modulators of inflammation and Inga laurina is a species that has an iSP (ILTi) in its seeds. The aim of this study was to evaluate the anti-inflammatory and antinociceptive response of this inhibitor. The assays performed were leukocyte infiltrate, mast cell degranulation, paw oedema, writhing abdominal, formalin and the determination of cytokines levels were the assays realized. Male Swiss mice, 18–25 g, were distributed in the groups Saline (10 mL/kg); Dexamethasone (0.5 mg/kg); ILTi (0.3; 3 or 30 mg/kg); Dipyrone (500 mg/kg), in the abdominal writhing assay and Morphine (5 mg/kg), in the formalin test. Cytokine levels were determined by flow cytometry. The results showed that ILTi (0.3 mg/kg) reduced the total leukocytes (64.5%) and polymorphonuclear cell infiltrate (74%), mast cell degranulation (30.2 ± 3.2%) and inhibited paw oedema in all times at the doses of 3 and 30 mg/kg. In addition, ILTi reduced IL-6 (35.6%) and TNF (79.2%) levels. In pain models, ILTi attenuated abdominal writhing (56.4%) and paw licking time in both phases (neurogenic, 43.2%; inflammatory, 23. 4%). Cytokine analysis revealed a decrease in IL-6 (35.6%) and TNF (79.2%) levels. These findings indicate that ILTi exhibits anti-inflammatory and antinociceptive effects, possibly through modulation of protease-mediated pathways or the blocking the activation of protease-activated receptors.