Therapeutic potential of hesperidin in diabetes mellitus-induced erectile dysfunction through Nrf2-mediated ferroptosis and oxidative stress.

IF 3.2 2区 医学 Q1 ANDROLOGY
Andrology Pub Date : 2024-11-25 DOI:10.1111/andr.13814
Sheng Xin, Wen Song, Jiaquan Mao, Peng Hu, Zhong Chen, Jihong Liu, Xiaodong Song, Qian Fang, Kai Cui
{"title":"Therapeutic potential of hesperidin in diabetes mellitus-induced erectile dysfunction through Nrf2-mediated ferroptosis and oxidative stress.","authors":"Sheng Xin, Wen Song, Jiaquan Mao, Peng Hu, Zhong Chen, Jihong Liu, Xiaodong Song, Qian Fang, Kai Cui","doi":"10.1111/andr.13814","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus-induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.</p><p><strong>Objectives: </strong>To elucidate the potential mechanism and efficacy of Hes in regulating Nrf2-mediated ferroptosis and oxidative stress in DMED.</p><p><strong>Materials and methods: </strong>DMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.</p><p><strong>Results: </strong>The results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase-1 (HO-1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG-induced HUVECs, Hes ameliorated Nrf2-mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.</p><p><strong>Conclusions: </strong>Hes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2-HO-1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Andrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/andr.13814","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANDROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus-induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.

Objectives: To elucidate the potential mechanism and efficacy of Hes in regulating Nrf2-mediated ferroptosis and oxidative stress in DMED.

Materials and methods: DMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.

Results: The results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase-1 (HO-1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG-induced HUVECs, Hes ameliorated Nrf2-mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.

Conclusions: Hes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2-HO-1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.

橙皮甙通过 Nrf2 介导的铁氧化作用和氧化应激对糖尿病诱发的勃起功能障碍的治疗潜力
背景:在代谢异常引起的勃起功能障碍(ED)中,糖尿病诱发的ED(DMED)进展迅速,症状严重,对常规药物的反应性降低。海绵体内的高血糖与诱导铁变态反应和氧化应激有关,而这两种反应都是由核因子 E2 相关因子 2(Nrf2)介导的。研究发现,黄酮类化合物橙皮甙(Hes)在某些糖尿病并发症中可激活 Nrf2,但橙皮甙对 DMED 的疗效和具体机制仍不清楚:阐明Hes在DMED中调节Nrf2介导的铁蛋白沉积和氧化应激的潜在机制和疗效:通过腹腔注射链脲佐菌素(STZ)构建DMED大鼠,部分补充Hes。同时,体外研究利用人体脐静脉内皮细胞(HUVECs),添加葡萄糖模拟高糖(HG)环境,并用 Hes 或 ML385(一种 Nrf2 抑制剂)诱导。收获阴茎组织和 HUVECs 进行后续分析:研究结果表明,Hes 可部分逆转受损的勃起功能。补充 Hes 后,阴茎海绵体中 Nrf2、谷胱甘肽过氧化物酶 4(GPX4)和血红素加氧酶-1(HO-1)的表达升高,从而抑制了铁变态反应和氧化应激。此外,勃起效应细胞的数量和功能得到恢复,海绵体纤维化也得到改善。在 HG 诱导的 HUVECs 中,Hes 可改善 Nrf2 介导的铁变态反应和氧化应激,而 ML385 可部分逆转这些效应:Hes对DMED大鼠有治疗作用,并对Nrf2-HO-1/GPX4轴有调节机制,同时可活化内皮细胞和平滑肌细胞,减轻纤维化。我们的研究为使用 Hes 治疗 DMED 提供了可靠的临床前证据。
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
Andrology
Andrology ANDROLOGY-
CiteScore
9.10
自引率
6.70%
发文量
200
期刊介绍: Andrology is the study of the male reproductive system and other male gender related health issues. Andrology deals with basic and clinical aspects of the male reproductive system (gonads, endocrine and accessory organs) in all species, including the diagnosis and treatment of medical problems associated with sexual development, infertility, sexual dysfunction, sex hormone action and other urological problems. In medicine, Andrology as a specialty is a recent development, as it had previously been considered a subspecialty of urology or endocrinology
×
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