Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Iranian Journal of Basic Medical Sciences Pub Date : 2025-01-01 DOI:10.22038/ijbms.2024.78864.17057

Ling Hu, Xiaoqiong Wei, Guofu Shen, Xiaohuan Huang

{"title":"Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury.","authors":"Ling Hu, Xiaoqiong Wei, Guofu Shen, Xiaohuan Huang","doi":"10.22038/ijbms.2024.78864.17057","DOIUrl":null,"url":null,"abstract":"Objectives: Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.Materials and methods: Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell infiltration (P<0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (P<0.01 and P<0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (P<0.01 and P<0.001), and inflammatory cytokines in brain tissue (P<0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell number (P<0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (P<0.05 and P<0.01), ASC mRNA level and IL-1β protein level (P<0.01), and IL-1β and IL-18 level in brain tissue (P<0.01) compared to positive control.Conclusion: EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"105-112"},"PeriodicalIF":2.1000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771333/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Basic Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.22038/ijbms.2024.78864.17057","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.

Materials and methods: Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.

Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell infiltration (P<0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (P<0.01 and P<0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (P<0.01 and P<0.001), and inflammatory cytokines in brain tissue (P<0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell number (P<0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (P<0.05 and P<0.01), ASC mRNA level and IL-1β protein level (P<0.01), and IL-1β and IL-18 level in brain tissue (P<0.01) compared to positive control.

Conclusion: EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.

查看原文本刊更多论文

鞣花酸可减轻NLRP6/caspase-1/ gsdmd介导的大鼠脑缺血再灌注损伤后的炎症和焦亡。

目的：鞣花酸（EA）是一种天然多酚，具有抗癌、抗氧化、抗炎、抗菌等作用。然而，EA在脑缺血再灌注损伤（CIRI）中的作用尚不清楚。本研究旨在探讨EA在CIRI中的神经保护作用。材料与方法：雄性Wistar大鼠40只（260 ~ 300 g），随机分为4组，每组10只：Sham+Veh：除不置入螺纹塞外，均行I/R手术，同时给予溶质处理。2) MCAO / R +阿明费。3) MCAO/R+EA：大鼠在MCAO前给予200 mg/kg EA。4) MCAO/R+Nim：大鼠在MCAO前给予Nim。结果：脑MCAO/R损伤脑组织，神经功能缺损评分升高（P0.01），脑梗死体积升高（P0.01），炎性细胞浸润升高（P0.01）， NLRP6、ASC、caspase-1、GSDMD mRNA水平升高（P0.01、P0.001）， NLRP6、caspase-1、GSDMD- n、IL-1β蛋白水平升高（P0.01、P0.001），脑组织炎症因子水平升高（P0.01）。与阳性对照组相比，预防给药EA可显著改善脑组织损伤，降低神经功能缺损评分（P0.01）、脑梗死体积（P0.01）、炎症细胞数量（P0.05）、脑组织NLRP6、caspase-1、GSDMD-N mRNA和蛋白水平（P0.05和P0.01）、ASC mRNA和IL-1β蛋白水平（P0.01）、IL-1β和IL-18水平（P0.01）。结论：EA可能是治疗脑I/R的潜在药物，其可能通过抑制炎性小体的激活而发挥抗炎作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY

CiteScore

4.00

自引率

4.50%

发文量

142

审稿时长

6-12 weeks

期刊介绍： The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.