东莨菪碱作为抗顺铂诱导的氧化应激和炎症的心脏保护剂

Q3 Pharmacology, Toxicology and Pharmaceutics

Phytomedicine Plus Pub Date : 2025-02-01 DOI:10.1016/j.phyplu.2025.100738

Esam Qnais , Omar Gammoh , Yousra Bsieso , Mohammad Alqudah , Mohammad Wedyan , Sara Altaber , Alaa A.A. Aljabali , Abdelrahim Alqudah , Taher Hatahet

{"title":"东莨菪碱作为抗顺铂诱导的氧化应激和炎症的心脏保护剂","authors":"Esam Qnais , Omar Gammoh , Yousra Bsieso , Mohammad Alqudah , Mohammad Wedyan , Sara Altaber , Alaa A.A. Aljabali , Abdelrahim Alqudah , Taher Hatahet","doi":"10.1016/j.phyplu.2025.100738","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity.</div></div><div><h3>Purpose</h3><div>The study aimed to explore the cardioprotective effects of scopoletin against CP-induced damage in mice, focusing on histopathological changes, cardiac biomarkers, oxidative stress, inflammation, apoptosis, and the modulation of key signaling pathways.</div></div><div><h3>Study Design</h3><div>A controlled experimental design was employed to evaluate scopoletin's efficacy in alleviating CP-induced cardiotoxicity, with dosing variations to assess dose dependency.</div></div><div><h3>Methods</h3><div>Male mice were allocated into five groups: a control group, a cisplatin-only group, two groups treated with low (50 mg/kg/day) and high doses (150 mg/kg/day) of scopoletin in conjunction with cisplatin, and a scopoletin-only group. The interventions were administered over a period of one week, with cardiac damage assessed through histopathological examinations, serum cardiac biomarker measurements, and analyses of oxidative stress, inflammatory cytokines, and apoptosis-related proteins. The efficacy of scopoletin in modulating the p62/Keap1/Nrf2 pathway was also examined.</div></div><div><h3>Results</h3><div>Histopathological assessments showed less tissue damage in scopoletin-treated groups (<em>p</em> < 0.01). Cardiac biomarkers were significantly lower in <span>l</span>- and H-scopoletin groups compared to the CP-only group (<em>p</em> < 0.05, <em>p</em> < 0.01). Scopoletin effectively reduced ROS and MDA levels while enhancing antioxidant enzymes like SOD, CAT, and GSH (<em>p</em> < 0.01). With scopoletin treatment, inflammatory cytokines TNF-α and IL-6 were notably reduced (<em>p</em> < 0.01). Apoptosis analysis revealed lower levels of pro-apoptotic proteins and higher levels of Bcl-2 in scopoletin groups (<em>p</em> < 0.05, <em>p</em> < 0.01). Significantly, scopoletin restored the function of the p62/Keap1/Nrf2 signaling pathway (<em>p</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>The findings suggest scopoletin's potential as an adjunctive therapy in cancer treatment to mitigate CP's adverse effects, warranting further clinical investigation.</div></div>","PeriodicalId":34599,"journal":{"name":"Phytomedicine Plus","volume":"5 1","pages":"Article 100738"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation\",\"authors\":\"Esam Qnais , Omar Gammoh , Yousra Bsieso , Mohammad Alqudah , Mohammad Wedyan , Sara Altaber , Alaa A.A. Aljabali , Abdelrahim Alqudah , Taher Hatahet\",\"doi\":\"10.1016/j.phyplu.2025.100738\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity.</div></div><div><h3>Purpose</h3><div>The study aimed to explore the cardioprotective effects of scopoletin against CP-induced damage in mice, focusing on histopathological changes, cardiac biomarkers, oxidative stress, inflammation, apoptosis, and the modulation of key signaling pathways.</div></div><div><h3>Study Design</h3><div>A controlled experimental design was employed to evaluate scopoletin's efficacy in alleviating CP-induced cardiotoxicity, with dosing variations to assess dose dependency.</div></div><div><h3>Methods</h3><div>Male mice were allocated into five groups: a control group, a cisplatin-only group, two groups treated with low (50 mg/kg/day) and high doses (150 mg/kg/day) of scopoletin in conjunction with cisplatin, and a scopoletin-only group. The interventions were administered over a period of one week, with cardiac damage assessed through histopathological examinations, serum cardiac biomarker measurements, and analyses of oxidative stress, inflammatory cytokines, and apoptosis-related proteins. The efficacy of scopoletin in modulating the p62/Keap1/Nrf2 pathway was also examined.</div></div><div><h3>Results</h3><div>Histopathological assessments showed less tissue damage in scopoletin-treated groups (<em>p</em> < 0.01). Cardiac biomarkers were significantly lower in <span>l</span>- and H-scopoletin groups compared to the CP-only group (<em>p</em> < 0.05, <em>p</em> < 0.01). Scopoletin effectively reduced ROS and MDA levels while enhancing antioxidant enzymes like SOD, CAT, and GSH (<em>p</em> < 0.01). With scopoletin treatment, inflammatory cytokines TNF-α and IL-6 were notably reduced (<em>p</em> < 0.01). Apoptosis analysis revealed lower levels of pro-apoptotic proteins and higher levels of Bcl-2 in scopoletin groups (<em>p</em> < 0.05, <em>p</em> < 0.01). Significantly, scopoletin restored the function of the p62/Keap1/Nrf2 signaling pathway (<em>p</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>The findings suggest scopoletin's potential as an adjunctive therapy in cancer treatment to mitigate CP's adverse effects, warranting further clinical investigation.</div></div>\",\"PeriodicalId\":34599,\"journal\":{\"name\":\"Phytomedicine Plus\",\"volume\":\"5 1\",\"pages\":\"Article 100738\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine Plus\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667031325000119\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine Plus","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667031325000119","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}

引用次数: 0

摘要

背景：顺铂（CP）是一种因其心脏毒性作用而臭名昭著的化疗药物。东莨菪素是一种天然香豆素，由于其抗氧化、抗炎和抗细胞凋亡的特性，可能会抵消cp诱导的心脏毒性。目的探讨东莨菪碱对cp诱导的小鼠心脏损伤的保护作用，主要从组织病理学改变、心脏生物标志物、氧化应激、炎症、凋亡以及关键信号通路的调节等方面进行研究。研究设计采用对照实验设计评估东莨菪碱减轻cp诱导的心脏毒性的疗效，并采用剂量变化来评估剂量依赖性。方法将小白鼠分为5组：对照组、单顺铂组、低剂量（50 mg/kg/d）、高剂量（150 mg/kg/d）东莨菪碱联合顺铂组和单剂量东莨菪碱组。干预为期一周，通过组织病理学检查、血清心脏生物标志物测量、氧化应激、炎症细胞因子和凋亡相关蛋白分析来评估心脏损伤。我们还研究了东莨菪素调节p62/Keap1/Nrf2通路的功效。结果组织病理学检查显示东莨菪碱治疗组大鼠组织损伤较小(p <；0.01)。与仅cp组相比，l-和h -东莨菪素组的心脏生物标志物显著降低(p <；0.05, p <；0.01)。东莨菪素能有效降低ROS和MDA水平，同时提高SOD、CAT和GSH等抗氧化酶水平(p <；0.01)。东莨菪素治疗后，炎性细胞因子TNF-α和IL-6显著降低(p <；0.01)。凋亡分析显示，东莨菪素组的促凋亡蛋白水平较低，Bcl-2水平较高(p <；0.05, p <；0.01)。值得注意的是，东莨菪素恢复了p62/Keap1/Nrf2信号通路的功能(p <；0.01)。结论东莨菪碱有可能作为肿瘤治疗的辅助药物，减轻CP的不良反应，值得进一步的临床研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation

查看原文本刊更多论文

Scopoletin as a cardioprotective agent against cisplatin-induced oxidative stress and inflammation

Background

Cisplatin (CP) is a chemotherapeutic agent notorious for its cardiotoxic effects. Scopoletin, a natural coumarin, has shown potential due to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which may counteract CP-induced cardiotoxicity.

Purpose

The study aimed to explore the cardioprotective effects of scopoletin against CP-induced damage in mice, focusing on histopathological changes, cardiac biomarkers, oxidative stress, inflammation, apoptosis, and the modulation of key signaling pathways.

Study Design

A controlled experimental design was employed to evaluate scopoletin's efficacy in alleviating CP-induced cardiotoxicity, with dosing variations to assess dose dependency.

Methods

Male mice were allocated into five groups: a control group, a cisplatin-only group, two groups treated with low (50 mg/kg/day) and high doses (150 mg/kg/day) of scopoletin in conjunction with cisplatin, and a scopoletin-only group. The interventions were administered over a period of one week, with cardiac damage assessed through histopathological examinations, serum cardiac biomarker measurements, and analyses of oxidative stress, inflammatory cytokines, and apoptosis-related proteins. The efficacy of scopoletin in modulating the p62/Keap1/Nrf2 pathway was also examined.

Results

Histopathological assessments showed less tissue damage in scopoletin-treated groups (p < 0.01). Cardiac biomarkers were significantly lower in l- and H-scopoletin groups compared to the CP-only group (p < 0.05, p < 0.01). Scopoletin effectively reduced ROS and MDA levels while enhancing antioxidant enzymes like SOD, CAT, and GSH (p < 0.01). With scopoletin treatment, inflammatory cytokines TNF-α and IL-6 were notably reduced (p < 0.01). Apoptosis analysis revealed lower levels of pro-apoptotic proteins and higher levels of Bcl-2 in scopoletin groups (p < 0.05, p < 0.01). Significantly, scopoletin restored the function of the p62/Keap1/Nrf2 signaling pathway (p < 0.01).

Conclusion

The findings suggest scopoletin's potential as an adjunctive therapy in cancer treatment to mitigate CP's adverse effects, warranting further clinical investigation.

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