Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-κB signaling pathway

被引:41
作者
Wang, Shaogui [1 ]
Yang, Zhiying [1 ]
Xiong, Fengxiao [1 ]
Chen, Cheng [1 ]
Chao, Xiaojuan [1 ]
Huang, Junying [1 ]
Huang, Heqing [1 ]
机构
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Diabetic nephropathy; Betulinic acid; NF-kappa B; Fibronectin; GLOMERULAR MESANGIAL CELLS; BETA-ARRESTINS; TRANSCRIPTION FACTORS; NEPHROPATHY; RECEPTOR; PATHOGENESIS; BETA-ARRESTIN2; COMPLICATIONS; FIBRONECTIN; DERIVATIVES;
D O I
10.1016/j.mce.2016.06.019
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin (FN), in the glomerular mesangium and tubulointerstitium. Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been demonstrated to have many pharmacological activities. However, the effect of BA on DN has not been fully elucidated. To explore the possible anti-inflammatory effects of BA and their underlying mechanisms, we used streptozotocin-induced diabetic rat kidneys and high glucose-treated glomerular mesangial cells. Our study showed BA could inhibit the degradation of I kappa B alpha and the activity of NF-kappa B in diabetic rat kidneys and high glucose-induced mesangial cells, resulting in reduction of FN expression. In addition, BA suppressed the DNA binding activity and transcriptional activity of NF-kappa B in high glucose-induced glomerular mesangial cells (GMCs). Furthermore, BA enhanced the interaction between I kappa B alpha and beta-arrestin2 in mesangial cells. Taken together, our data suggest BA inhibits NF-kappa B activation through stabilizing NF-kappa B inhibitory protein I kappa B alpha, thereby preventing diabetic renal fibrosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:135 / 143
页数:9
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