Chlorfortunone A alleviates kidney fibrosis in diabetic nephropathy mice via modulating the TGF-β/Smad2 pathway
10.3760/cma.j.cn311282-20240815-00358
- VernacularTitle:Chlorfortunone A通过调节TGF-β/Smad2通路抑制糖尿病肾病小鼠肾纤维化
- Author:
Jianmei BAI
1
;
Yingzhe LIU
1
;
Ruixue TIAN
1
;
Rongshan LI
1
;
Lin ZHANG
1
;
Baodong WANG
1
Author Information
1. 山西省人民医院、山西医科大学第五临床医学院肾内科，太原 030012
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathy;
Fibrosis;
Chlorfortunone A;
TGF-β;
Smad2
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(2):145-151
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect and mechanism of Chlorfortunone A(ChlA) in the treatment of diabetic nephropathy(DN) in mice.Methods:The DN model mice were assigned to DN, low-dose ChlA(ChlAL) and high-dose ChlA(ChlAH), and the normal control groups(Ctrl). Kidney tissue was analyzed via HE and Masson staining, and urine albumin, fasting blood glucose and kidney weight were measured. Collagen1 and α-SMA proteins were detected in renal tissues. The level of GSH-px, SOD, CAT, and TGF-β were detected. The TGF-β/Smad2 pathway in kidney tissue was detected. The mechanism was verified by setting the high glucose+ ChlA+ TGF-β group in MPC-5 cells. The proliferation of the cells and DCFDA staining were detected.Results:Compared to the Ctrl group, the DN group had significantly higher UACR and kidney weight( P<0.001). High-dose ChlA reduced UACR and kidney weight( P<0.05), with no effect on blood glucose( P>0.05). Masson staining showed reduced fibrosis with ChlA treatment. Collagen I and α-SMA expressions were significantly higher in DN( P<0.001) and decreased with ChlA treatment( P<0.05). GSH-px, SOD, and CAT levels were lower in DN( P<0.001), while TGF-β was elevated( P<0.001); ChlA increased antioxidant enzymes and decreased TGF-β( P<0.05). The TGF-β/Smad2 pathway was upregulated in DN( P<0.001) and inhibited by ChlA( P<0.001). In vitro, ChlA reduced cell proliferation( P<0.05) and increased ROS levels( P<0.001). Conclusions:ChlA alleviates kidney injury and fibrosis in DN mice, reduces oxidative stress, which may be related to the inhibition of the TGF-β/Smad2 pathway.
