Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii.
BACKGROUND
Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation.


METHODS
Anti-inflammatory effects of celastrol (0-1 microM) were examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. To investigate the effects of celastrol (0-50 microg per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model.


RESULTS
Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E(2), but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264.7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines.


CONCLUSIONS
Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases.
Kim
D H
DH
Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Korea.
Shin
E K
EK
Kim
Y H
YH
Lee
B W
BW
Jun
J-G
JG
Park
J H Y
JH
Kim
J-K
JK
D000818:Animals; D000529:Complementary Therapies; D004487:Edema / Q000188:drug therapy; D007150:Immunohistochemistry; D045563:Indolequinones / Q000008:administration & dosage / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D018078:Receptors, Prostaglandin E / Q000187:drug effects*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014315:Triterpenes / Q000008:administration & dosage / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D045563:Indolequinones; D018836:Inflammation Mediators; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014315:Triterpenes; C068040:quinone methide; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; C050414:celastrol