A novel synthetic dibenzocyclooctadiene lignan analog XLYF-104-6 attenuates lipopolysaccharide-induced inflammatory response in RAW264.7 macrophage cells and protects BALB/c mice from sepsis

详细信息    查看全文

• 作者：Chunping Gu^a ; Fang-Lin Yu^b ; Le Yu^a ; Xiao-Yang He^b ; Desheng Zhong^a ; Longgang He^a ; Longyun Lv^a ; Lan Xie^b ; Shuwen Liu^a ; ^{liusw@smu.edu.cn" class="auth_mail}
• 关键词：BAY 11-7082 (Pubchem CID ; 5353431) ; Lipopolysaccharide (Pubchem CID ; 11970143) ; MTT (Pubchem CID ; 64965) ; DAPI (Pubchem CID ; 2954) ; G418 (Pubchem CID ; 123865) ; PMSF (Pubchem CID ; 4784) ; Leupeptin (Pubchem CID ; 72429) ; Pepstatin (Pubchem CID ; 5478883) ; Sodium fluoride (Pubchem CID ; 5235) ; Aprotinin (Pubchem CID ; 16130295)
• 刊名：European Journal of Pharmacology
• 出版年：15 April, 2014
• 年：2014
• 卷：729
• 期：Complete
• 页码：22-29
• 全文大小：1480 K

文摘

The wide range of inflammation mechanisms under control by NF-魏B makes this pathway as an attractive target for new anti-inflammatory drugs. Herein, we showed that a new dibenzocyclooctadiene lignan analog XLYF-104-6, with a chemical name of 1,2,3,10,11-pentamethoxydibenzocycloocta-6,7-[c] pyrrole-1,3-dione, inhibited lipopolysaccharide (LPS)-induced NF-魏B activation in RAW264.7 cells through preventing I魏B伪 degradation and p65 nuclear translocation. The inhibitory activity of this compound on NF-魏B activation contributes to the reduction of LPS-induced TNF-伪 and IL-6 productions. Notably, XLYF-104-6 suppressed LPS-induced iNOS expression and NO production in a NF-魏B independent manner, since IKK inhibitor BAY 11-7082 has failed to exert similar inhibitory effect on iNOS expression and NO production. In addition, XLFY-104-6 also exerted anti-inflammatory action in endotoxemic mice by decreasing plasma LPS-induced TNF-伪 and IL-1尾 levels as well as increasing plasma LPS-induced IL-10 concentrations. These findings suggest XLYF-104-6 could act as a leading compound for developing a potential anti-inflammatory drug.