Ursolic acid reduces inflammation and fibrosis in the kidney of diabetic mice

熊果酸 糖尿病肾病 纤维化 炎症 糖尿病 尾加压素Ⅱ 医学 内科学 肾小球硬化 肾脏疾病 链脲佐菌素 内分泌学 药理学 足细胞 化学 蛋白尿 受体 色谱法
作者
SA Manea,AG Lazar,ML Vlad,Andrei Manea
出处
期刊:Cardiovascular Research [Oxford University Press]
卷期号:118 (Supplement_1)
标识
DOI:10.1093/cvr/cvac066.225
摘要

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UEFISCDI Background Diabetic kidney disease (DKD) is arguably the major disabling and life-threatening microvascular-related disorder associated with both type I and type II diabetes. Inflammation of glomerular capillary system and progressive accumulation of glomerular extracellular proteins are important culprit mechanisms leading to glomerulosclerosis and ultimately renal failure in end-stage DKD. Conventional anti-diabetic therapies can only delay the progression of DKD. The naturally-occurring triterpenic acids emerged as important candidate pharmacological compounds for the treatment of cardiometabolic disorders. Purpose We aimed at investigating the potential regulatory effects of ursolic acid, a pentacyclic triterpenoid, on the expression of key pro-inflammatory and pro-fibrotic mediators in diabetic kidney. Methods Non-diabetic and streptozotocin-induced diabetic C57BL/6J male mice were randomized to receive via intraperitoneal injection 1 mg/kg ursolic acid (UA), or its vehicle (5% DMSO + 95% PBS, pH 7.4), for 4 weeks. Human endothelial cells (EC) were exposed to normal (5 mM) or high (25mM) concentration of glucose in the absence/presence of 1-10 μM UA. Real-time PCR, Western blot, and immunofluorescence microscopy techniques were employed to investigate the expression of selected DKD-relevant pro-inflammatory and pro-fibrotic molecules. Morphological aspects of the kidney and glomeruli were assessed by histochemistry. Results The mRNA/protein levels of pro-inflammatory (MCP-1, TNFα, NOS2, ICAM-1, VCAM-1, E-selectin) and pro-fibrotic (collagen IV, fibronectin, laminin, TGFβ) mediators were found significantly elevated in the kidney of diabetic mice as compared to non-diabetic counterparts. Treatment of diabetic mice with UA significantly reduced the up-regulated expression of pro-inflammatory mediators, extracellular matrix proteins, and pro-fibrotic factor TGFβ. Moreover, glomerular hypertrophy and the up-regulation of glomerular collagen IV, fibronectin, and laminin protein levels were significantly reduced in UA-treated diabetic mice. In cultured human EC, UA suppressed the high glucose-induced up-regulation of ICAM-1, VCAM-1, E-selectin and NF-kB signaling. Conclusion In experimental diabetes, ursolic acid down-regulates the expression of DKD-relevant pro-inflammatory and pro-fibrotic molecules in the kidney of diabetic mice by potentially targeting NF-kB signaling pathway. The data of this study suggest that triterpenic acids and their chemical derivates could become important pharmacological tools to reduce inflammation and fibrosis associated with DKD.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
花雨落123完成签到,获得积分20
刚刚
dylaner发布了新的文献求助10
1秒前
乐乐应助枯木逢春采纳,获得10
1秒前
zonghonghan发布了新的文献求助10
1秒前
烟花应助shenxian82133采纳,获得10
2秒前
SYLH应助Master采纳,获得20
3秒前
舒伯特完成签到 ,获得积分10
3秒前
4秒前
万能图书馆应助Steven采纳,获得10
4秒前
李某发布了新的文献求助10
4秒前
花雨落123发布了新的文献求助10
5秒前
5秒前
5秒前
8秒前
张超完成签到,获得积分10
8秒前
无算浮白发布了新的文献求助10
10秒前
古丁完成签到,获得积分10
13秒前
阔达的满天完成签到,获得积分10
13秒前
雪梨101完成签到 ,获得积分10
13秒前
PRIPRO发布了新的文献求助10
14秒前
14秒前
15秒前
赘婿应助Steven采纳,获得10
15秒前
情怀应助科研通管家采纳,获得10
16秒前
我是老大应助科研通管家采纳,获得10
16秒前
16秒前
英俊的铭应助科研通管家采纳,获得10
16秒前
华仔应助科研通管家采纳,获得10
16秒前
我是老大应助科研通管家采纳,获得10
16秒前
科研通AI5应助科研通管家采纳,获得10
16秒前
16秒前
华仔应助科研通管家采纳,获得10
16秒前
领导范儿应助科研通管家采纳,获得10
17秒前
共享精神应助科研通管家采纳,获得10
17秒前
英俊的铭应助科研通管家采纳,获得10
17秒前
Akim应助科研通管家采纳,获得10
17秒前
SciGPT应助科研通管家采纳,获得10
17秒前
17秒前
天天快乐应助科研通管家采纳,获得10
17秒前
17秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3976177
求助须知:如何正确求助?哪些是违规求助? 3520366
关于积分的说明 11202745
捐赠科研通 3256847
什么是DOI,文献DOI怎么找? 1798509
邀请新用户注册赠送积分活动 877704
科研通“疑难数据库(出版商)”最低求助积分说明 806516