Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway

被引:9
|
作者
Li, Jialin [1 ,2 ]
Zhang, Jiawen [3 ]
Yang, Meng [3 ]
Huang, Xiaocui [3 ]
Zhang, Meng [3 ]
Fang, Xiansong [4 ]
Wu, Suzhen [1 ,3 ]
机构
[1] Gannan Med Univ, Key Lab Prevent & Treatment Cardiovasc & Cerebrov, Minist Educ, Ganzhou, Peoples R China
[2] Gannan Med Univ, Sch Pharm, Ganzhou, Peoples R China
[3] Gannan Med Univ, Sch Basic Med, 1 Yixueyuan Rd, Ganzhou 341000, Peoples R China
[4] Gannan Med Univ, Affiliated Hosp 1, Ganzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
TNF-alpha; IL-6; mesangial cells; fibronectin; collagen IV; MESANGIAL CELLS; FIBROSIS; BETA; INFLAMMATION; FIBRONECTIN; ACTIVATION; MECHANISMS; EXPRESSION; GLIMPSE;
D O I
10.1080/13880209.2022.2112239
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Context: Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated. Objective: This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms. Materials and methods: The mesangial cells were treated with 20 mu M kirenol and 10 ng/mL human recombinant TGE-beta 1 or 30mM glucose for 24h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups (n=10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n=10) was included as the control. Results: Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-kappa B (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of I kappa B alpha was restored to normal level by kirenol treatment both in vivo and in vitro. After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-alpha expression was decreased 0.34- and 0.46-fold, in vitro and in vivo, respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion. Discussion and conclusions: Kirenol could alleviate DN by downregulating the TGF-beta/Smads and the NE-kappa B signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.
引用
收藏
页码:1690 / 1700
页数:11
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