Inflexin attenuates proinflammatory responses and nuclear factor-kappaB activation in LPS-treated microglia.
Activated microglia participate in neuroinflammation which contribute to neuronal damage. Suppression of microglial activation would have therapeutic benefits, which lead to alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of inflexin, a putative antiinflammatory agent isolated from Isodon excisus (Max.) Kudo (Labiateae), on the production of proinflammatory mediators were investigated in the lipopolysaccharide (LPS)-stimulated microglia. Inflexin significantly inhibited the release of nitric oxide (NO). Consistently, both the mRNA and the protein levels for the inducible NO synthase were decreased by inflexin in a concentration-dependent manner. Inflexin also inhibited the expression of cyclooxygenase (COX)-2, but not the COX-1 and effectively reduced the LPS-induced expression of proinflammatory cytokines in a dose-dependent manner. Furthermore, inflexin inhibited the degradation of IkappaB-alpha and the activation of NF-kappaB, p65 and Akt, while the MAPKs signal pathway was not affected. Our data suggest that inflexin was able to suppress neuroinflammation via inhibition of NF-kappaB activation and Akt pathway indicating that inflexin may be developed as a potent therapeutic agent in treating neuroinflammatory diseases.
Department of Biotechnology, Konkuk University, Chungju, 380-701, South Korea.
Hyun Myung
HM
Ko
Sushruta
S
Koppula
Byung-Wook
BW
Kim
In Su
IS
Kim
Bang Yeon
BY
Hwang
Kyoungho
K
Suk
Eun Jung
EJ
Park
Dong-Kug
DK
Choi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D045786:Diterpenes, Kaurane; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C530049:ent-1,3,6,11-tetrahydroxykaur-16-ene-15-one 3,11-diacetate; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases