Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
| Autor: | Byung-Wook Kim, Seong-Mook Kang, Dong-Kug Choi, Hyung-Woo Lim, Sandeep Vasant More, Sushruta Koppula, Sung-Hwa Yoon, Ju-Young Park, Hemant Kumar |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide medicine.medical_treatment Central nervous system Active Transport Cell Nucleus Pharmacology p38 Mitogen-Activated Protein Kinases Cell Line Nitric oxide Mice chemistry.chemical_compound Cannabinoid receptor type 2 medicine Animals Phosphorylation Neuroinflammation Cell Nucleus Inflammation Microglia Cannabinoids Chemistry lcsh:RM1-950 NF-kappa B Protein Subunits lcsh:Therapeutics. Pharmacology Neuroprotective Agents medicine.anatomical_structure Pyrazoles Molecular Medicine Tumor necrosis factor alpha Cannabinoid Inflammation Mediators Signal Transduction |
| Zdroj: | Journal of Pharmacological Sciences, Vol 121, Iss 2, Pp 119-130 (2013) |
| ISSN: | 1347-8648 1347-8613 |
| Popis: | 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. Keywords:: lipopolysaccharide, microglia, neuroinflammation, cannabinoid signaling |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|