4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study
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 neuropro...
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Shahid Beheshti University of Medical Sciences
2024-09-01
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| Series: | Archives of Academic Emergency Medicine |
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| Online Access: | https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2456 |
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| author | Hamzeh Mirshekari Jahangiri Alireza Moradi Donya Nazarinia Nahid Aboutaleb |
| author_facet | Hamzeh Mirshekari Jahangiri Alireza Moradi Donya Nazarinia Nahid Aboutaleb |
| author_sort | Hamzeh Mirshekari Jahangiri |
| collection | DOAJ |
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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 assigned 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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| format | Article |
| id | doaj-art-3a620f71ba2e4188893df186ad2f454b |
| institution | OA Journals |
| issn | 2645-4904 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Shahid Beheshti University of Medical Sciences |
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| series | Archives of Academic Emergency Medicine |
| spelling | doaj-art-3a620f71ba2e4188893df186ad2f454b2025-08-20T01:55:19ZengShahid Beheshti University of Medical SciencesArchives of Academic Emergency Medicine2645-49042024-09-0113110.22037/aaem.v13i1.24564-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental StudyHamzeh Mirshekari JahangiriAlireza MoradiDonya NazariniaNahid Aboutaleb0IRAN UNIVERSITY OF MEDICAL SCIENCES 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 assigned 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. https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2456Ischemic stroke4-methylumbilliferonInflammationTLR4/NF-κB/NLRP3 pathwaynerve function |
| spellingShingle | Hamzeh Mirshekari Jahangiri Alireza Moradi Donya Nazarinia Nahid Aboutaleb 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study Archives of Academic Emergency Medicine Ischemic stroke 4-methylumbilliferon Inflammation TLR4/NF-κB/NLRP3 pathway nerve function |
| title | 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study |
| title_full | 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study |
| title_fullStr | 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study |
| title_full_unstemmed | 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study |
| title_short | 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study |
| title_sort | 4 methylumbilliferon 4 mu as a potential treatment against cerebral ischemia and reperfusion injury in rats an experimental study |
| topic | Ischemic stroke 4-methylumbilliferon Inflammation TLR4/NF-κB/NLRP3 pathway nerve function |
| url | https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2456 |
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