A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-kappa B and JNK MAPK signaling in microglial BV2 cells

作者：Cai Bangrong; Seong Kyung Joo; Bae Sun Woong; Chun Changju; Kim Won Jae^*; Jung Ji Yeon^*

来源：International Immunopharmacology, 2018, 61: 204-214.

DOI：10.1016/j.intimp.2018.05.021

• Diosgenin derivative
• MAPK
• Microglia
• Neuroinflammation
• NF-kappa B

Diosgenin, a precursor of steroid hormones in plants, is known to exhibit diverse pharmacological activities including anti-inflammatory properties. In this study, (3 beta, 25R)-spirost-5-en-3-oxyl (2-((2((2-aminoethyl)amino)ethyl)amino)ethyl) carbamate (DGP), a new synthetic diosgenin derivative incorporating primary amine was used to investigate its anti-inflammatory effects and underlying mechanisms of action in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Pretreatment with DGP resulted in significant inhibition of nitric oxide (NO) synthesis, and down-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated microglial BV2 cells. In addition, DGP decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha). The inhibitory effects of DGP on these inflammatory mediators in LPS-stimulated microglial BV2 cells were regulated by NF-kappa B signaling through blocking p65 nuclear translocation and NF-kappa B p65/DNA binding activity. DGP also blocked the phosphorylation of c-Jun amino-terminal kinase (JNK), but not p38 kinase or extracellular signal regulated kinases (ERK). The NF-kappa B inhibitor JSH-23 and JNK-specific inhibitor SP600125 significantly decreased NO production and IL-6 release in LPS-stimulated BV2 cells, respectively. The overall results demonstrate that DGP has anti-inflammatory effects on LPS-stimulated BV2 cells via inhibition of NF-kappa B and JNK activation, suggesting that DGP is a potential prophylactic agent in various neurodegenerative disorders.

• 出版日期2018-8