Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy

IF 6.9 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Biomedicine & Pharmacotherapy Pub Date : 2024-09-30 DOI:10.1016/j.biopha.2024.117499
Juan Chen , Zi-yun Hu , Yu Ma , Shan Jiang , Jiu-yu Yin , Yu-kai Wang , Yong-gui Wu , Xue-qi Liu
{"title":"Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy","authors":"Juan Chen ,&nbsp;Zi-yun Hu ,&nbsp;Yu Ma ,&nbsp;Shan Jiang ,&nbsp;Jiu-yu Yin ,&nbsp;Yu-kai Wang ,&nbsp;Yong-gui Wu ,&nbsp;Xue-qi Liu","doi":"10.1016/j.biopha.2024.117499","DOIUrl":null,"url":null,"abstract":"<div><div>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 (<em>Euodia rutaecarpa</em> (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.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117499"},"PeriodicalIF":6.9000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicine & Pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0753332224013854","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

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.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
芦他卡品通过靶向 CK2α 减轻糖尿病肾病的炎症和纤维化
糖尿病肾病(DN)是糖尿病严重的微血管并发症之一。在糖尿病肾病的发展过程中,肾小球系膜细胞(GMCs)的增殖导致过多的细胞外基质(ECM)在系膜区域沉积,最终导致肾小球硬化。芦根碱(Rut)是一种生物碱,存在于传统中药材枸杞子(Euodia rutaecarpa (Juss.) Benth.)中,具有多种生物活性。然而,它在 DN 中的作用机制仍然未知。本研究使用 db/db 小鼠和高糖(HG)处理的小鼠间质细胞(SV40 MES-13)来评估芦根对 DN 中 GMC 的保护作用及其潜在机制。我们发现,路得能减轻尿白蛋白和肾功能,明显缓解肾脏病理损伤。此外,路得还能减少 ECM 的产生和肾脏炎症,并抑制 TGF-β1/Smad3 和 NF-κB 信号通路在体外和体内的激活。通过靶点预测、分子对接、细胞热转移试验(CETSA)和表面等离子体共振(SPR),蛋白激酶CK2α(CK2α)被确定为Rut的靶点。此外,沉默 CK2α 后,Rut 无法继续在经 HG 处理的 SV40 细胞中发挥保护作用。综上所述,本研究首次发现 Rut 可通过抑制 TGF-β1/Smad3 和 NF-κB 信号通路的激活以及靶向 CK2α 来抑制经 HG 处理的 SV40 细胞中 ECM 的生成和炎症反应。因此,Rut 有可能成为一种治疗 DN 的新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
11.90
自引率
2.70%
发文量
1621
审稿时长
48 days
期刊介绍: Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
期刊最新文献
Enhancing lung cancer growth inhibition with calcium ions: Role of mid- and high-frequency electric field pulses Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway The possible role of hypoxia-induced exosomes on the fibroblast metabolism in idiopathic pulmonary fibrosis Inhibition of breast cancer growth with AN-329, a novel Hsp110 inhibitor, by inactivating p-STAT3/c-Myc axis Synthesis, characterisation, and anti-tumour activity of nano-immuno-conjugates for enhanced photodynamic therapy of oesophageal cancer stem cells
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1