2. Academic Validation
  3. Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation

Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation

  • Biochim Biophys Acta Mol Basis Dis. 2024 Feb 13:167056. doi: 10.1016/j.bbadis.2024.167056.
Jing Luo 1,  Yujia Luo 2,  Jialei Chen 3,  Yu Gao 4,  Junyi Tan 5,  Yongkang Yang 6,  Changhong Yang 7,  Ning Jiang 8,  Yong Luo 9
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Pathology, Chongqing Medical University, Chongqing, China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, China; Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, China; Department of Pathology and Pathophysiology, Chongqing Medical University, Chongqing, China.
  • 4 Department of Pathology, Chongqing Medical University, Chongqing, China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, China; Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 5 Department of Pathology and Pathophysiology, Chongqing Medical University, Chongqing, China.
  • 6 Department of Clinical Medicine, Clinical Medical College of Chengdu University, Chengdu, China.
  • 7 Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
  • 8 Department of Pathology, Chongqing Medical University, Chongqing, China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, China; Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
  • 9 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 38360072 DOI: 10.1016/j.bbadis.2024.167056
Abstract

Our previous research suggests that targeting NLRP3 inflammasomes holds promise for mitigating cerebral ischemia/reperfusion injury. The gut metabolite Urolithin B (UroB) has been shown to inhibit the neuroinflammation. However, the specific role of UroB in cerebral ischemia/reperfusion injury and its potential impact on NLRP3 inflammasome remain unclear. In this study, acute stroke was simulated using the MCAO model in male Sprague-Dawley rats. UroB was intraperitoneally administered after 1 h of reperfusion. The effects of UroB on brain tissue were evaluated, including infarct volume, brain edema, and neurobehavioral changes. Western blotting and immunofluorescence were performed to investigate the effect of UroB on inflammation-related proteins. Furthermore, TRIM65 knockdown and TXNIP overexpression experiments elucidated the role of UroB in NLRP3 inflammasome activation. The ( demonstrate the neuroprotective effect of UroB in acute stroke, reducing brain tissue damage and improving motor function. Mechanistically, UroB modulated neuroinflammation by influencing TXNIP and TRIM65 protein expression, as well as competitive binding to the NLRP3 inflammasome, attenuating cerebral ischemia/reperfusion injury. In conclusion, the potential of UroB as a protective agent against cerebral ischemia/reperfusion injury in acute stroke stands out as it regulates TRIM65 and TXNIP competitive binding to the NLRP3 inflammasome. These findings suggest that UroB is a promising drug candidate for the treatment of acute stroke.

Keywords

Cerebral ischemia/reperfusion; NLRP3 inflammasome; Neuroinflammation; TRIM65; TXNIP; UroB.

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