4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study.

IF 2.9 Q1 EMERGENCY MEDICINE Archives of Academic Emergency Medicine Pub Date : 2024-09-17 eCollection Date: 2025-01-01 DOI:10.22037/aaem.v13i1.2456

Hamzeh Mirshekari Jahangiri, Alireza Moradi, Donya Nazarinia, Nahid Aboutaleb

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Abstract

Introduction: Ischemic stroke (IS) is one of the three main fatal disorders and is a major health challenge. 4-methylumbelliferone (4-MU) is one of the coumarin derivatives (7-hydroxy-4-methylcoumarin) with antioxidant and anti-inflammatory impact. This study was conducted to elucidate the neuroprotective effects and anti-inflammatory impact of 4-MU in a rodent model of IS.

Methods: The IS model was induced by middle cerebral artery occlusion (MCAO) for 1 hour and reperfusion was established for 24 hours. 44 Male Wistar rats were divided into four groups: 1) Sham, 2) MCAO, 3) MCAO + Vehicle, and 4) MCAO + 4-MU (25 mg/kg). Evaluation of neurological deficit was performed using Garcia's score. 2,3,5-triphenoyl-2H-tetrazolium chloride (TTC) staining was employed to measure infarct size. Nissl staining was applied to determine neuronal loss. Moreover, western blotting was utilized to detect the expression of the proteins relevant to the TLR4/NF-κB/NLRP3 axis (p-NF-κB p65, TLR4, NLRP3, IL-1β, IL-10, IL-18, ASC, and Caspase-1).

Results: It was observed that MCAO caused neurological deficit (P<0.0001), infarct (P<0.0001), and neuronal loss (P<0.002); up-regulated NLRP3 (P<0.0001), TLR4 (P<0.0001), p-NF-κB p65 (P<0.0005), IL-1β (P<0.0014), IL-18 (P<0.0001), ASC (P<0.0027), and Caspase-1 (P<0.0052); and reduced IL-10 concentrations (P<0.0024). Administration of 4-MU (25 mg/kg) quickly after reperfusion reduced neurological deficit (P<0.0001), infarct size (P<0.0001), neuronal loss (P<0.0058), and down-regulated NLRP3 (P<0.0257), TLR4 (P<0.0001), p-NF-κB p65 (P<0.0075), IL-1β (P<0.0106), IL-18 (P<0.0005), ASC (P<0.0072), and Caspase-1 (P<0.0315), and increased IL-10 concentrations (P<0.0215).

Conclusion: These results indicate that 4-MU can attenuate injury after MCAO by suppressing the TLR4/NF-κB/NLRP3 axis. Our findings show that 4-MU can be considered a novel therapeutic compound to cure IS.

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4-methylumbilliferon (4-MU) 作为大鼠脑缺血和再灌注损伤的一种潜在治疗方法；一项实验研究。

简介缺血性中风（IS）是三大致命疾病之一，也是一项重大的健康挑战。4-甲基伞形酮（4-MU）是香豆素衍生物（7-羟基-4-甲基香豆素）之一，具有抗氧化和抗炎作用。本研究旨在阐明 4-MU 在啮齿动物 IS 模型中的神经保护作用和抗炎影响：方法：大脑中动脉闭塞（MCAO）诱导 IS 模型 1 小时，再灌注 24 小时。44 雄性 Wistar 大鼠分为四组：1）Sham 组；2）MCAO 组；3）MCAO + 车辆组；4）MCAO + 4-MU 组（25 毫克/千克）。采用加西亚评分法评估神经功能缺损情况。采用 2,3,5-三苯甲酰基-2H-氯化四氮唑（TTC）染色法测量梗死面积。Nissl染色用于确定神经元的损失。此外，还利用 Western 印迹法检测与 TLR4/NF-κB/NLRP3 轴相关的蛋白质（p-NF-κB p65、TLR4、NLRP3、IL-1β、IL-10、IL-18、ASC 和 Caspase-1）的表达：结果：观察到 MCAO 导致神经功能缺损（PC）：这些结果表明，4-MU 可通过抑制 TLR4/NF-κB/NLRP3 轴来减轻 MCAO 后的损伤。我们的研究结果表明，4-MU 可被视为一种治疗 IS 的新型化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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