Ribemansides A and B, TRPC6 Inhibitors from Ribes manshuricum That Suppress TGF-β1-Induced Fibrogenesis in HK-2 Cells

被引:13
|
作者
Zhou, Baoping [1 ]
Wang, Yange [1 ]
Zhang, Chunlei [1 ]
Yang, Guolin [1 ]
Zhang, Fan [1 ]
Yu, Boyang [1 ]
Chai, Chengzhi [1 ]
Cao, Zhengyu [1 ]
机构
[1] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCM Pharmacol, Nanjing 211198, Jiangsu, Peoples R China
来源
JOURNAL OF NATURAL PRODUCTS | 2018年 / 81卷 / 04期
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; KIDNEY FIBROSIS; CHANNELS; PATHWAYS; SEED;
D O I
10.1021/acs.jnatprod.7b01037
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Two new acylated beta-hydroxynitrile glycosides, ribemansides A (1) and B (2), were isolated from the aerial parts of Ribes manshuricum. Their structures were elucidated by comprehensive spectroscopic analysis. Ribemansides A and B inhibited transforming growth factor beta 1 (TGF-beta 1)-induced expression of alpha-smooth muscle actin, fibronectin release, and changes in cell morphology in the human proximal tubular epithelial cell line (human kidney-2, HK-2). Further biological evaluation demonstrated that both 1 and 2 inhibit the activity of canonical transient receptor potential cation channel 6 (TRPC6), with IC50 values of 24.5 and 25.6 mu M, respectively. The antifibrogenic effect of these compounds appears to be mediated through TRPC6 inhibition, since the TRPC6 inhibitor, SAR7334, also suppressed TGF-beta 1-induced fibrogenesis in HK-2 cells.
引用
收藏
页码:913 / 917
页数:5
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