The anti-inflammatory effects of N-methyl-(2S,4R)-trans-4-hydroxyl -L-proline from Syderoxylon obtusifolium are related to its inhibition of TNF-alpha and inflammatory enzymes

Background: Sideroxylon obtusifolium (Roem. & Schult.) T.D. Penn., Sapotaceae family, is a medicinal species native to the Brazilian Northeastern region. The plant is popularly used as an anti-inflammatory and hypoglycemic. Purpose: To evaluate the anti-inflammatory properties of the N-methyl-(2S,4R)-trans-4-hydroxy-l-proline (NMP) from S. obtusifolium leaves in models of inflammation and to clarify its action mechanisms. Methods: Male Swiss mice were distributed intocontrols and groups treated with NMP (25, 50 and 100 mg/ kg, p.o.), indomethacin or morphine (reference drugs). The animals were subjected to the formalin, carrageenan-induced edema and peritonitis tests. Furthermore, peritoneal lavage and slices from edematous paws were used for histological and immunohistochemical (iNOS, TNF-alpha, COX-2 and NFkB) assays. Results: Decreases in licking time, in the 1st and mainly in the 2nd phases of the formalin test, were shown after NMP treatments. In addition, decreases (around 50%) in paw edema were noticed at the 3rd h. The HE staining of paw slices demonstrated a complete reversion of the increased PMN cell number-after NMP treatment. Similarly, decreases higher than 70% were also demonstrated in PMN cells, in the peritoneal fluid. Furthermore, NMP significantly decreased iNOS, TNF-alpha, COX-2 and NF-kB immuno-reactivities. Conclusions: We showed that S. obtusifolium presents a potent anti-inflammatory activity, due to the presence of the N-methyl-(2S, 4R)-trans-4-hydroxy-l-proline(NMP) in the plant extract. This action is related to the inhibition by NMP of TNF-alpha and inflammatory enzymes. (C) 2016 Elsevier GmbH. All rights reserved.