@article{APS7849,
author = {Yongwoo Jung and Se Eun Byeon and Dae Sung Yoo and Yong Gyu Lee and Tao Yu and Yanyan Yang and Ji Hye Kim and Eunji Kim and Deok Jeong and Man Hee Rhee and Eui Su Choung and Sungyoul Hong and Jae Youl Cho},
title = {8-(Tosylamino)quinoline inhibits macrophage-mediated inflammation by suppressing NF-κB signaling},
journal = {Acta Pharmacologica Sinica},
volume = {33},
number = {8},
year = {2016},
keywords = {},
abstract = {Aim: The macrophage-mediated inflammatory response may contribute to the development of cancer, diabetes, atherosclerosis and septic shock. This study was to characterize several new compounds to suppress macrophage-mediated inflammation.
Methods: Peritoneal macrophages from C57BL/6 male mice and RAW264.7 cells were examined. Anti-inflammatory activity was evaluated in the cells exposed to lipopolysaccharide (LPS). The mechanisms of the anti-inflammatory activity were investigated via measuring transcription factor activation in response to specific signals and via assaying the activities of the target kinases.
Results: Of 7 candidate compounds tested, 8-(tosylamino)quinoline (8-TQ, compound 7) exhibited the strongest activities in suppressing the production of NO, TNF-α, and PGE2 in LPS-activated RAW264.7 cells and peritoneal macrophages (the IC50 values=1−5 μmol/L). This compound (1.25−20 μmol/L) dose-dependently suppressed the expression of the pro-inflammatory genes for iNOS, COX-2, TNF-α, and the cytokines IL-1β and IL-6 at the level of transcription in LPS-activated RAW264.7 cells. 8-TQ (20 μmol/L) significantly suppressed the activation of NF-κB and its upstream signaling elements, including inhibitor of κB (IκBα), IκBα kinase (IKK) and Akt in LPS-activated RAW264.7 cells. In in vivo experiments, oral administration of 20 and 40 mg/kg 8-TQ for 3 d significantly alleviated the signs of LPS-induced hepatitis and HCl/EtOH-induced gastritis, respectively, in ICR mice.
Conclusion: 8-TQ (compound 7) exerts significant anti-inflammatory activity through the inhibition of the Akt/NF-κB pathway, thus may be developed as a novel anti-inflammatory drug.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7849}
}