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东莨菪亭对链脲佐菌素诱导的糖尿病大鼠氧化应激和心脏功能障碍的治疗效果。

Therapeutic efficacy of scopoletin on oxidative stress and cardiac dysfunction in streptozotocin-induced diabetic rats.

作者信息

Alqudah Abdelrahim, Qnais Esam, Gammoh Omar, Bseiso Yousra, Wedyan Mohammed, Shilbayeh Sireen Abdul Rahim, Abudalo Rawan, Oqal Muna, Aljabali Alaa A A

机构信息

Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.

Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa, Jordan.

出版信息

Am J Med Sci. 2025 Jun 13. doi: 10.1016/j.amjms.2025.06.010.

DOI:10.1016/j.amjms.2025.06.010
PMID:40518075
Abstract

BACKGROUND

Cardiac dysfunction associated with diabetes often arises as a serious condition, primarily driven by persistent oxidative imbalance and chronic inflammation. There are few treatments for such complication and therefore, there is considerable interest in natural compounds such as scopoletin has antioxidative and anti-inflammatory activities. This study investigates how scopoletin may influence disease progression in a rat model of diabetic cardiomyopathy induced by streptozotocin (STZ).

METHODS

Thirty-two male Wistar rats were evenly distributed into four study groups using a randomization protocol: a non-diabetic control, an untreated diabetic group, a diabetic group administered scopoletin, and a diabetic group treated with metformin (Glucophage) as a reference therapy. Post-diabetes induction by streptozotocin, treatments were administered for three weeks, subsequently, malondialdehyde (MDA) concentrations were measured along with, the enzymatic activities of key cardiac antioxidants-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were evaluated to assess oxidative defense status. ATPase activities, gene expression (p53 and VCAM-1), and histopathological examinations of heart tissues.

RESULTS

Scopoletin treatment significantly reduced MDA levels by up to 35 %, with p < 0.01 compared to the diabetic control. Antioxidant enzyme activities were notably enhanced, with increases in SOD, CAT, and GPx activities by approximately 50 % (p < 0.01). Cardiac ATPase activities showed marked improvement (p < 0.05), and the expression of p53 and VCAM-1 was effectively downregulated (p < 0.01). Histopathological analysis revealed substantial reductions in myocardial damage, vacuolation, and tissue congestion in scopoletin-treated groups, with the high-dose effects comparable to those observed with metformin (Glucophage).

CONCLUSIONS

Scopoletin demonstrates significant potential in treating diabetic cardiomyopathy. These results encourage further clinical trials to explore scopoletin as a complementary therapy for cardiac complications in diabetic patients.

摘要

背景

与糖尿病相关的心脏功能障碍通常是一种严重疾病,主要由持续的氧化失衡和慢性炎症驱动。针对这种并发症的治疗方法很少,因此,人们对具有抗氧化和抗炎活性的天然化合物如东莨菪素颇感兴趣。本研究调查了东莨菪素如何影响链脲佐菌素(STZ)诱导的糖尿病性心肌病大鼠模型中的疾病进展。

方法

32只雄性Wistar大鼠采用随机分组方案平均分为四个研究组:非糖尿病对照组、未治疗的糖尿病组、给予东莨菪素的糖尿病组以及用二甲双胍(格华止)作为参考治疗的糖尿病组。链脲佐菌素诱导糖尿病后,进行为期三周的治疗,随后测量丙二醛(MDA)浓度,并评估关键心脏抗氧化剂超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的酶活性,以评估氧化防御状态。检测心脏组织的ATP酶活性、基因表达(p53和VCAM-1)以及组织病理学检查。

结果

与糖尿病对照组相比,东莨菪素治疗使MDA水平显著降低高达35%,p<0.01。抗氧化酶活性显著增强,SOD、CAT和GPx活性增加约50%(p<0.01)。心脏ATP酶活性显著改善(p<0.05),p53和VCAM-1的表达有效下调(p<0.01)。组织病理学分析显示,东莨菪素治疗组的心肌损伤、空泡形成和组织充血显著减少,高剂量组的效果与二甲双胍(格华止)相当。

结论

东莨菪素在治疗糖尿病性心肌病方面显示出巨大潜力。这些结果鼓励进一步开展临床试验,以探索将东莨菪素作为糖尿病患者心脏并发症的辅助治疗方法。

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