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α-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

α-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

Kyoung-Goo Lee, Suel-Gie Lee, Hwi-Ho Lee, Hae Jun Lee, Ji-Sun Shin, Nan-Jung Kim, Hyo-Jin An, Jung-Hwan Nam, Dae Sik Jang, Kyung-Tae Lee

Chem Biol Interact. 2015 Jun 25;235:85-94.

PMID: 25913072

Abstract:

In this study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of α-chaconine in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in LPS-induced septic mice. α-Chaconine inhibited the expressions of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) at the transcriptional level, and attenuated the transcriptional activity of activator protein-1 (AP-1) by reducing the translocation and phosphorylation of c-Jun. α-Chaconine also suppressed the phosphorylation of TGF-β-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 α-chaconine-mediated inhibition of pro-inflammatory mediators. In a sepsis model, pretreatment with α-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 α-chaconine are associated with the suppression of AP-1, and support its possible therapeutic role for the treatment of sepsis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP20562032	α-Chaconine		20562-03-2	Price

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