alpha-Chaconine isolated from a Solanum tuberosum L. cv Jayoung suppresses lipopolysaccharide-induced pro-inflammatory mediators via AP-1 inactivation in RAW 264.7 macrophages and protects mice from endotoxin shock

作者：Lee Kyoung Goo; Lee Suel Gie; Lee Hwi Ho; Lee Hae Jun; Shin Ji Sun; Kim Nan Jung; An Hyo Jin; Nam Jung Hwan; Jang Dae Sik; Lee Kyung Tae^*

来源：Chemico-Biological Interactions, 2015, 235: 85-94.

DOI：10.1016/j.cbi.2015.04.015

• alpha-Chaconine
• Inflammatory mediators
• MKK7
• Sepsis
• AP-1

In this study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of alpha-chaconine in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in LPS-induced septic mice. alpha-Chaconine inhibited the expressions of cyclooxygenase-2 (COX-2), interleukin-10 (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) at the transcriptional level, and attenuated the transcriptional activity of activator protein-1 (AP-1) by reducing the translocation and phosphorylation of c-Jun. alpha-Chaconine also suppressed the phosphorylation of TGF-beta-activated kinase-1 (TAK1), which lies upstream of mitogen-activated protein kinase kinase 7 (MKK7)/Jun N-terminal kinase (JNK) signaling. JNK knockdown using siRNA prevented the alpha-chaconine-mediated inhibition of pro-inflammatory mediators. In a sepsis model, pretreatment with alpha-chaconine reduced the LPS-induced lethality and the mRNA and production levels of pro-inflammatory mediators by inhibiting c-Jun activation. These results suggest that the anti-inflammatory effects of alpha-chaconine are associated with the suppression of AP-1, and support its possible therapeutic role for the treatment of sepsis.

• 出版日期2015-6-25