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.
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.


OBJECTIVE
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 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.


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 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.


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.
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil.
Pedro Everson Alexandre
PE
de Aquino
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil.
Talita Rocha
TR
Magalhães
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil.
Lucas Antônio Duarte
LA
Nicolau
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil.
Luzia Kalyne A Moreira
LK
Leal
Department of Organic and Inorganic Chemistry of the Federal University of Ceará, Ceará, Brazil.
Nayara Coriolano
NC
de Aquino
Department of Organic and Inorganic Chemistry of the Federal University of Ceará, Ceará, Brazil.
Sabrina Matias
SM
Dos Santos
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil.
Kelly Rose Tavares
KR
Neves
Department of Organic and Inorganic Chemistry of the Federal University of Ceará, Ceará, Brazil.
Edilberto Rocha
ER
Silveira
Faculty of Medicine of the Federal University of Ceará (UFC), Ceará, Brazil; Faculty of Medicine Estácio of Juazeiro do Norte (FMJ), Ceará, Brazil. Electronic address: gbviana@live.com.
Glauce Socorro de Barros
GS
Viana
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D029632:Sapotaceae / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha
Cytokines; Inflammation; Oxidative stress; Sideroxylon obtusifolium