Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy.

Autor: Chen J; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Hu ZY; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Ma Y; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Jiang S; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Yin JY; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Wang YK; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China., Wu YG; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China; Center for Scientific Research of Anhui Medical University, Hefei, Anhui 230022, PR China. Electronic address: wuyonggui@medmail.com.cn., Liu XQ; Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China. Electronic address: liuxueqi0309@163.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Nov; Vol. 180, pp. 117499. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1016/j.biopha.2024.117499
Abstrakt: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae (Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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