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

Abstract Serine proteases (SP) are a defense mechanism for neutrophil, 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) modulate inflammation and can be found in the Fabaceae family. Inga laurina, for exemple, is a species that has an iSP (ILTi) in its seeds.To evaluate the anti-inflammatory and antinociceptive response of a protease inhibitor purified of Inga laurina seeds (ILTi). Leukocyte infiltrate, mast cell degranulation, paw edema, writhing abdominal, formalin and determination of cytokines levels were the assays realized. Male Swiss mice, 18-25g, 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 writhing abdominal 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 inhibit paw edema in all times at the doses 3 and 30 mg/kg. In addition, ILTi reduced IL-6 (35.6%) and TNF (79.2%) levels. In antinociceptive evaluation ILTi reduced abdominal writhing (56.4%) and paw licking time at the both phases (neurogenic, 43.2%; inflammatory, 23. 4%). ILTi has anti-inflammatory and antinociceptive effects probably due to inhibition of inflammatory proteases or blocking the activation of protease-activated receptors.