13-Ethylberberine reduces HMGB1 release through AMPK activation in LPS-activated RAW264.7 cells and protects endotoxemic mice from organ damage

详细信息    查看全文

• 作者：Dong Ung Lee^c ; ¹ ; Young Shin Ko^a ; ¹ ; Hye Jung Kim^a ; ^b ; Ki Churl Chang^a ; ^b ; ^{kcchang@gnu.kr}
• 关键词：BBR ; berberine ; CLP ; cecal ligation and puncture ; HMGB1 ; high mobility group box 1 ; HO-1 ; heme oxygenase-1 ; iNOS ; inducible nitric oxide synthase ; LPS ; lipopolysaccharide ; NF-κB ; Nuclear factor kappa B ; NO ; nitric oxide ; siRNA ; small interfering RNA ; H&E ; hematoxylin and eosin ; PCNA ; proliferating cell nuclear antigen ; DMEM ; dulbecco&rsquo ; s modified eagle&rsquo ; s medium ; FBS ; fatal bovine serum ; AMPK ; AMP-activated protein kinase ; 13-EBR ; 13-ethylberberine ; TNF-α ; tumor necrosis factor-alpha ; I
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：86
• 期：Complete
• 页码：48-56
• 全文大小：2150 K
• 卷排序：86

文摘

High mobility group box 1 (HMGB1), a highly conserved non-histone DNA-binding protein, plays an important role in the pathogenesis of sepsis. Previously, the authors reported 13-ethylberberine (13-EBR) has anti-inflammatory and antibacterial effects. However, the effect of 13-EBR on HMGB1 release was not investigated. In the present study, it was hypothesized 13-EBR might reduce HMGB1 release by activating AMPK under septic conditions. The results obtained showed 13-EBR significantly reduced HMGB1 release from LPS-activated RAW264.7 cells, and that this reduction was reversed by silencing p38, or AMPK, or by co-treating cells with p38 MAPKinase inhibitor. 13-EBR increased the phosphorylations of p38 and AMPK, and the phosphorylation of p38 by 13-EBR was inhibited by AMPK-siRNA, indicating AMPK acted upstream of p38. In the lung tissues of LPS-treated mice, 13-EBR administration significantly increased p-AMPK but reduced inducible nitric oxide synthase (iNOS) protein levels. Hematoxylin and eosin staining revealed 13-EBR significantly reduced LPS-induced lung and liver damage. In addition, 13-EBR inhibited NF-kB in LPS-activated RAW264.7 cells, and in LPS-treated mice, 13-EBR administration significantly increased survival. Furthermore, co-administration of 13-EBR plus LPS prevented LPS-induced aortic rings hypocontractile response to phenylephrine in vitro. Taken together, these results indicate 13-EBR might offer a means of treating sepsis through AMPK activation.