Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats.

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI:10.1177/09603271251322186
Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma
{"title":"Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats.","authors":"Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma","doi":"10.1177/09603271251322186","DOIUrl":null,"url":null,"abstract":"<p><p>IntroductionDiabetic cardiomyopathy (DCM) is a complication of diabetes mellitus (DM) that can lead to heart failure and increase the risk of mortality. Pedunculoside (PE), a novel triterpenoid saponin, exhibits anti-inflammatory and anti-oxidative stress (OS) properties. However, its role in DCM remains unexplored.MethodsDCM models were established and treated with PE or the Nrf2 inhibitor (ML385). In vitro, cell function was evaluated using CCK-8, flow cytometry, qRT-PCR, and ELISA. In vivo, fasting blood glucose and insulin levels in rats were measured. The effects of PE on DCM were assessed using HE staining, TUNEL staining, and corresponding kits. Additionally, Nrf2/HO-1 pathway proteins were analyzed by western blot.ResultsLow doses of PE (2.5, 5, 10, and 20 μM) did not affect the viability of H9c2 cells. PE (10 and 20 μM) improved cell viability and prevented apoptosis, inflammation, and OS in high glucose (HG)-stimulated H9c2 cells. PE also upregulated Nrf2 in the nucleus and enhanced HO-1 and NQO1 expression in HG-treated H9c2 cells. Furthermore, the Nrf2 inhibitor (ML385) reversed PE's protective effects on HG-induced cell injury. In vivo, PE reduced blood glucose, increased insulin, alleviated myocardial injury, inhibited apoptosis, decreased levels of inflammatory factors and OS, and upregulated Nrf2, HO-1, and NQO1 in DCM model rats.DiscussionPE alleviates DCM injury by activating the Nrf2/HO-1 pathway. These findings support the potential therapeutic application of PE in DCM.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251322186"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human & experimental toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/09603271251322186","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/11 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

IntroductionDiabetic cardiomyopathy (DCM) is a complication of diabetes mellitus (DM) that can lead to heart failure and increase the risk of mortality. Pedunculoside (PE), a novel triterpenoid saponin, exhibits anti-inflammatory and anti-oxidative stress (OS) properties. However, its role in DCM remains unexplored.MethodsDCM models were established and treated with PE or the Nrf2 inhibitor (ML385). In vitro, cell function was evaluated using CCK-8, flow cytometry, qRT-PCR, and ELISA. In vivo, fasting blood glucose and insulin levels in rats were measured. The effects of PE on DCM were assessed using HE staining, TUNEL staining, and corresponding kits. Additionally, Nrf2/HO-1 pathway proteins were analyzed by western blot.ResultsLow doses of PE (2.5, 5, 10, and 20 μM) did not affect the viability of H9c2 cells. PE (10 and 20 μM) improved cell viability and prevented apoptosis, inflammation, and OS in high glucose (HG)-stimulated H9c2 cells. PE also upregulated Nrf2 in the nucleus and enhanced HO-1 and NQO1 expression in HG-treated H9c2 cells. Furthermore, the Nrf2 inhibitor (ML385) reversed PE's protective effects on HG-induced cell injury. In vivo, PE reduced blood glucose, increased insulin, alleviated myocardial injury, inhibited apoptosis, decreased levels of inflammatory factors and OS, and upregulated Nrf2, HO-1, and NQO1 in DCM model rats.DiscussionPE alleviates DCM injury by activating the Nrf2/HO-1 pathway. These findings support the potential therapeutic application of PE in DCM.

在高糖诱导的H9c2细胞和糖尿病性心肌病模型大鼠中,足跖草苷通过Nrf2/HO-1途径抑制心肌细胞炎症生物标志物。
糖尿病性心肌病(DCM)是糖尿病(DM)的一种并发症,可导致心力衰竭并增加死亡风险。pedculloside (PE)是一种新型的三萜皂苷,具有抗炎和抗氧化应激的特性。然而,它在DCM中的作用仍未被探索。方法建立sdcm模型,分别用PE或Nrf2抑制剂ML385处理。体外用CCK-8、流式细胞术、qRT-PCR和ELISA评价细胞功能。在体内,测量了大鼠的空腹血糖和胰岛素水平。采用HE染色、TUNEL染色及相应试剂盒评估PE对DCM的影响。western blot检测Nrf2/HO-1通路蛋白。结果2.5、5、10、20 μM慢剂量PE对H9c2细胞活力无影响。PE (10 μM和20 μM)可提高高糖(HG)刺激的H9c2细胞的活力,防止细胞凋亡、炎症和OS。在hg处理的H9c2细胞中,PE还上调了细胞核中的Nrf2,增强了HO-1和NQO1的表达。此外,Nrf2抑制剂(ML385)逆转了PE对hg诱导的细胞损伤的保护作用。在体内,PE可降低DCM模型大鼠的血糖,升高胰岛素,减轻心肌损伤,抑制细胞凋亡,降低炎症因子和OS水平,上调Nrf2、HO-1和NQO1。pe通过激活Nrf2/HO-1通路减轻DCM损伤。这些发现支持PE在DCM中的潜在治疗应用。
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 求助全文
来源期刊
自引率
0.00%
发文量
0
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信