Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Journal of Pharmacological Sciences

Hemant Kumar¹  Hyung-Woo Lim¹  Seong-Mook Kang¹  Sung-Hwa Yoon²  Byung-Wook Kim¹  Sandeep Vasant More¹  Sushruta Koppula¹  Dong-Kug Choi¹  Ju-Young Park² 

[1] Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Korea;Department of Molecular Science and Technology, Ajou University, Korea

关键词: lipopolysaccharide;    microglia;    neuroinflammation;    cannabinoid signaling;   

DOI  :  10.1254/jphs.12170FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(78)Cited-By(14)Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition. In the present study, we synthesized and investigated a novel CB derivative (CD-101) for its ability to suppress lipopolysaccharide (LPS)-mediated activation of BV-2 microglial cells and subsequent release of various inflammatory mediators. CD-101 significantly inhibited the production of inflammatory markers such as nitric oxide, cyclooxygenase-2, and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. The anti-neuroinflammatory effect of this novel cannabinoid derivative occurred by inhibiting p38MAPK phosphorylation and by decreasing nuclear translocation of p65 subunit of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. These results suggest that the use of the cannabinoid derivative CD-101 might be a potential therapeutic target against neuroinflammatory disorders.

【 授权许可】

Unknown