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

de Aquino, Pedro Everson Alexandre, Magalhães, Talita Rocha, Nicolau, Lucas Antônio Duarte, Leal, Luzia Kalyne A. Moreira, de Aquino, Nayara Coriolano, dos Santos, Sabrina Matias, Neves, Kelly Rose Tavares, Silveira, Edilberto Rocha, Viana, Glauce Socorro de Barros
Phytomedicine 2017 v.24 pp. 14-23
Sideroxylon, anti-inflammatory activity, edema, formalin, formalin test, immunohistochemistry, indigenous species, indomethacin, inducible nitric oxide synthase, inflammation, leaves, mice, models, morphine, peritonitis, plant extracts, staining, transcription factor NF-kappa B, tumor necrosis factor-alpha
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.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.Male Swiss mice were distributed intocontrols and groups treated with NMP (25, 50 and 100mg/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 NF-kB) assays.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 numberafter 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 immunoreactivities.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.