非靶向代谢组学研究表明,丁香通过激活ATF-6/CHOP/NF-κB信号轴减轻糖尿病大鼠内质网应激和氧化还原损伤。

IF 2.9 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
3 Biotech Pub Date : 2025-10-01 Epub Date: 2025-09-19 DOI:10.1007/s13205-025-04523-y
Karan Singh Yadav, Gurvinder Singh, Anjali Mishra, Amol Chhatrapati Bisen, Akash Ranjan, Rabi Sankar Bhatta, Vineeta Tripathi, Dinesh Kumar, Madhav Nilakanth Mugale
{"title":"非靶向代谢组学研究表明,丁香通过激活ATF-6/CHOP/NF-κB信号轴减轻糖尿病大鼠内质网应激和氧化还原损伤。","authors":"Karan Singh Yadav, Gurvinder Singh, Anjali Mishra, Amol Chhatrapati Bisen, Akash Ranjan, Rabi Sankar Bhatta, Vineeta Tripathi, Dinesh Kumar, Madhav Nilakanth Mugale","doi":"10.1007/s13205-025-04523-y","DOIUrl":null,"url":null,"abstract":"<p><p>This study reports the therapeutic potential of aqueous seed extract <i>Syzygium cumini</i> (AESC) in alleviating type 1 diabetes mellitus (T1DM) associated endoplasmic reticulum (ER) and oxidative stress in a streptozotocin (STZ)-induced rat model. The LC-MS/MS analysis of AESC revealed gallic acid, ellagic acid, quercetin, malic acid, and citric acid as major antidiabetic phytoconstituents. Administration of AESC (250 mg/kg) normalized fasting blood glucose levels to those of healthy control rats. Moreover, AESC increases antioxidant levels and downregulates ER and inflammatory markers. Histopathological evaluation showed improved pancreatic tissue architecture, and immunohistochemistry revealed enhanced insulin expression within the islets. Mechanistically, AESC alleviated ER stress and oxidative damage through the ATF-6/CHOP/NF-κB signaling axis. Furthermore, serum metabolomics indicated aberrant accumulation of branched-chain amino acids and reduced 3-hydroxybutyrate levels (increased ketolysis) in diabetic rats that were reversed by AESC. This study is limited by using a single dosage of AESC and short-term evaluation, emphasizing acute rather than long-term effects. Furthermore, the lack of in vitro validation and genetic knockdown approaches restricts confirmation of the specific mechanisms underlying the antidiabetic action of the extract. Future studies employing multiple dosage regimens, chronic treatment models, and molecular validation strategies are warranted to establish the long-term efficacy, safety, and mechanistic specificity of AESC as a potential therapeutic for T1DM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13205-025-04523-y.</p>","PeriodicalId":7067,"journal":{"name":"3 Biotech","volume":"15 10","pages":"356"},"PeriodicalIF":2.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449296/pdf/","citationCount":"0","resultStr":"{\"title\":\"Untargeted metabolomics reveals <i>Syzygium cumini</i> (L.) alleviates ER stress and redox damage via activation of ATF-6/CHOP/NF-κB signaling axis in diabetic rats.\",\"authors\":\"Karan Singh Yadav, Gurvinder Singh, Anjali Mishra, Amol Chhatrapati Bisen, Akash Ranjan, Rabi Sankar Bhatta, Vineeta Tripathi, Dinesh Kumar, Madhav Nilakanth Mugale\",\"doi\":\"10.1007/s13205-025-04523-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study reports the therapeutic potential of aqueous seed extract <i>Syzygium cumini</i> (AESC) in alleviating type 1 diabetes mellitus (T1DM) associated endoplasmic reticulum (ER) and oxidative stress in a streptozotocin (STZ)-induced rat model. The LC-MS/MS analysis of AESC revealed gallic acid, ellagic acid, quercetin, malic acid, and citric acid as major antidiabetic phytoconstituents. Administration of AESC (250 mg/kg) normalized fasting blood glucose levels to those of healthy control rats. Moreover, AESC increases antioxidant levels and downregulates ER and inflammatory markers. Histopathological evaluation showed improved pancreatic tissue architecture, and immunohistochemistry revealed enhanced insulin expression within the islets. Mechanistically, AESC alleviated ER stress and oxidative damage through the ATF-6/CHOP/NF-κB signaling axis. Furthermore, serum metabolomics indicated aberrant accumulation of branched-chain amino acids and reduced 3-hydroxybutyrate levels (increased ketolysis) in diabetic rats that were reversed by AESC. This study is limited by using a single dosage of AESC and short-term evaluation, emphasizing acute rather than long-term effects. Furthermore, the lack of in vitro validation and genetic knockdown approaches restricts confirmation of the specific mechanisms underlying the antidiabetic action of the extract. Future studies employing multiple dosage regimens, chronic treatment models, and molecular validation strategies are warranted to establish the long-term efficacy, safety, and mechanistic specificity of AESC as a potential therapeutic for T1DM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13205-025-04523-y.</p>\",\"PeriodicalId\":7067,\"journal\":{\"name\":\"3 Biotech\",\"volume\":\"15 10\",\"pages\":\"356\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449296/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"3 Biotech\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1007/s13205-025-04523-y\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"3 Biotech","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s13205-025-04523-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

本研究报道了黄籽水提取物(AESC)在链脲佐菌素(STZ)诱导的大鼠模型中缓解1型糖尿病(T1DM)相关内质网(ER)和氧化应激的治疗潜力。hplc -MS/MS分析显示没食子酸、鞣花酸、槲皮素、苹果酸和柠檬酸是抗糖尿病的主要植物成分。给予AESC (250 mg/kg)使空腹血糖水平恢复到健康对照大鼠水平。此外,AESC增加抗氧化水平,下调内质网和炎症标志物。组织病理学评估显示胰腺组织结构改善,免疫组织化学显示胰岛内胰岛素表达增强。机制上,AESC通过ATF-6/CHOP/NF-κB信号轴减轻内质网应激和氧化损伤。此外,血清代谢组学表明,在AESC逆转的糖尿病大鼠中,支链氨基酸的异常积累和3-羟基丁酸水平的降低(酮解增加)。本研究的局限性在于使用单一剂量的AESC和短期评估,强调急性而非长期效果。此外,缺乏体外验证和基因敲低方法限制了对提取物抗糖尿病作用的具体机制的确认。未来有必要采用多剂量方案、慢性治疗模型和分子验证策略进行研究,以确定AESC作为T1DM潜在治疗方法的长期有效性、安全性和机制特异性。补充信息:在线版本包含补充资料,下载地址:10.1007/s13205-025-04523-y。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Untargeted metabolomics reveals Syzygium cumini (L.) alleviates ER stress and redox damage via activation of ATF-6/CHOP/NF-κB signaling axis in diabetic rats.

This study reports the therapeutic potential of aqueous seed extract Syzygium cumini (AESC) in alleviating type 1 diabetes mellitus (T1DM) associated endoplasmic reticulum (ER) and oxidative stress in a streptozotocin (STZ)-induced rat model. The LC-MS/MS analysis of AESC revealed gallic acid, ellagic acid, quercetin, malic acid, and citric acid as major antidiabetic phytoconstituents. Administration of AESC (250 mg/kg) normalized fasting blood glucose levels to those of healthy control rats. Moreover, AESC increases antioxidant levels and downregulates ER and inflammatory markers. Histopathological evaluation showed improved pancreatic tissue architecture, and immunohistochemistry revealed enhanced insulin expression within the islets. Mechanistically, AESC alleviated ER stress and oxidative damage through the ATF-6/CHOP/NF-κB signaling axis. Furthermore, serum metabolomics indicated aberrant accumulation of branched-chain amino acids and reduced 3-hydroxybutyrate levels (increased ketolysis) in diabetic rats that were reversed by AESC. This study is limited by using a single dosage of AESC and short-term evaluation, emphasizing acute rather than long-term effects. Furthermore, the lack of in vitro validation and genetic knockdown approaches restricts confirmation of the specific mechanisms underlying the antidiabetic action of the extract. Future studies employing multiple dosage regimens, chronic treatment models, and molecular validation strategies are warranted to establish the long-term efficacy, safety, and mechanistic specificity of AESC as a potential therapeutic for T1DM.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04523-y.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
3 Biotech
3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)
CiteScore
6.00
自引率
0.00%
发文量
314
期刊介绍: 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.
×
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:604180095
Book学术官方微信