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...
| Publicado en: | Archives of Academic Emergency Medicine Vol. 13; no. 1; pp. 1 - 11 |
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| Autores principales: | , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Shahid Beheshti University of Medical Sciences
2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=190500665&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 190500665 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 26454904 MFMK jtl: Archives of Academic Emergency Medicine issn: 26454904 maglogo: N pubinfo: dt: 2025 vid: 13 iid: 1 pid: 87963 pub: Shahid Beheshti University of Medical Sciences artinfo: ui: 190500665 190500665 190500665 10.22037/aaem.v13i1.2456 190500665 ppf: 1 ppct: 10 formats: fmt: @attributes: type: P tig: atl: 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study. aug: au: Mirshekari Jahangiri, Hamzeh Moradi, Alireza Nazarinia, Donya Aboutaleb, Nahid affil: Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. sug: subj: Cerebral Ischemia Drug Therapy Reperfusion Injury Drug Therapy Benzopyrans Analogs and Derivatives Neuroprotective Agents Therapeutic Use Antiinflammatory Agents Therapeutic Use Treatment Outcomes Evaluation Animal Studies Rats Experimental Studies Funding Source Gastrointestinal Agents Neuroprotective Agents Administration and Dosage Staining and Labeling Blotting, Western Interleukins Intercellular Signaling Peptides and Proteins Caspases Gene Expression Random Assignment Descriptive Statistics Post Hoc Analysis Data Analysis Software ab: 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-KB/NLRP3 axis (p–NF–KB 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–KB 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–KB 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). Conclusions: These results indicate that 4-MU can attenuate injury after MCAO by suppressing the TLR4/NF-KB/NLRP3 axis. Our findings show that 4-MU can be considered a novel therapeutic compound to cure IS. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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