Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury
Objective(s): 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 CIR...
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Mashhad University of Medical Sciences
2025-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25031_ae4c6740428568aeb07d87ea54ce5d3a.pdf |
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| author | Ling Hu Xiaoqiong Wei Guofu Shen Xiaohuan Huang |
| author_facet | Ling Hu Xiaoqiong Wei Guofu Shen Xiaohuan Huang |
| author_sort | Ling Hu |
| collection | DOAJ |
| description | Objective(s): 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. |
| format | Article |
| id | doaj-art-2d1cbd1a3ba748469675e0bda9f1faf4 |
| institution | DOAJ |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-2d1cbd1a3ba748469675e0bda9f1faf42025-08-20T03:08:50ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-01-0128110511210.22038/ijbms.2024.78864.1705725031Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injuryLing Hu0Xiaoqiong Wei1Guofu Shen2Xiaohuan Huang3Department of Pathology, Chongqing Three Gorges Medical College, Wanzhou, ChinaChongqing Three Gorges Medical College, Wanzhou, ChinaChongqing Three Gorges Medical College, Wanzhou, ChinaDepartment of Pathology, Chongqing Three Gorges Medical College, Wanzhou, ChinaObjective(s): 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.https://ijbms.mums.ac.ir/article_25031_ae4c6740428568aeb07d87ea54ce5d3a.pdfcerebral ischemia/reperfusion injuryellagic acidinflammationnlrp6 inflammasomepyroptosis |
| spellingShingle | Ling Hu Xiaoqiong Wei Guofu Shen Xiaohuan Huang Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury Iranian Journal of Basic Medical Sciences cerebral ischemia/reperfusion injury ellagic acid inflammation nlrp6 inflammasome pyroptosis |
| title | Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury |
| title_full | Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury |
| title_fullStr | Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury |
| title_full_unstemmed | Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury |
| title_short | Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury |
| title_sort | ellagic acid alleviates nlrp6 caspase 1 gsdmd mediated inflammation and pyroptosis in rats post cerebral ischemia reperfusion injury |
| topic | cerebral ischemia/reperfusion injury ellagic acid inflammation nlrp6 inflammasome pyroptosis |
| url | https://ijbms.mums.ac.ir/article_25031_ae4c6740428568aeb07d87ea54ce5d3a.pdf |
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