Inflexin attenuates proinflammatory responses and nuclear factor-κB activation in LPS-treated microglia

• Published in: European journal of pharmacology Vol. 633; no. 1; pp. 98 - 106
• Main Authors: Ko, Hyun Myung, Koppula, Sushruta, Kim, Byung-Wook, Kim, In Su, Hwang, Bang Yeon, Suk, Kyoungho, Park, Eun Jung, Choi, Dong-Kug
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.2010; Elsevier
• Subjects: Biological and medical sciences; BV2 cell; COX-2; Inflexin; iNOS; LPS; Medical sciences; Microglia; NF-κB; Pharmacology. Drug treatments; Inflexin; NF-κB; COX-2; iNOS; BV2 cell; LPS; Microglia; Enzyme; Neuroglia; Cyclooxygenase 2; Inflammation; In vitro; Nitric-oxide synthase; Lipopolysaccharide; Oxidoreductases; Transcription factor NFκB
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.02.011

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 IκB-α and the activation of NF-κB, 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-κB activation and Akt pathway indicating that inflexin may be developed as a potent therapeutic agent in treating neuroinflammatory diseases.