2. Academic Validation
  3. Methyl isoeugenol suppresses NLRP3 inflammasome-mediated pyroptosis via activation of Nrf2/NQO1/HO-1 signaling in cerebral ischemia-reperfusion injury

Methyl isoeugenol suppresses NLRP3 inflammasome-mediated pyroptosis via activation of Nrf2/NQO1/HO-1 signaling in cerebral ischemia-reperfusion injury

  • Biochem Pharmacol. 2025 Jul:237:116947. doi: 10.1016/j.bcp.2025.116947.
Huina Liu 1,  Weitao Chen 1,  Meiyuan He 1,  Linlin Nie 1,  Yaru Pan 2,  Danni Guan 2,  Yongyi Li 2,  Ting Wan 3,  Lining Duan 3,  Cong Yang 2,  Weirong Li 2,  Qi Wang 4,  Lixing Zhuang 5,  Yifan Zhang 6
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405 Guangdong, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
  • 2 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
  • 3 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405 Guangdong, China.
  • 4 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address: [email protected].
  • 5 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405 Guangdong, China. Electronic address: [email protected].
  • 6 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405 Guangdong, China; Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405 Guangdong, China. Electronic address: [email protected].
PMID: 40228641 DOI: 10.1016/j.bcp.2025.116947
Abstract

Microglial neuroinflammation is considered to be a vital injury factor aggravating ischemia-reperfusion (I/R) injury on the progression of cerebral ischemic stroke. Mounting evidences have verified the effect of Pyroptosis mediated by NLRP3 inflammasome on modulating microglial phenotype, and maintaining the microglial M1/M2 phenotype balance could be a novel target to ameliorate cerebral I/R injury. Herein, we focused on the anti-neuroinflammatory effect of methyl isoeugenol, a bioactive compound isolated from Acorus tatarinowii Schott, on nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated NLRP3 inflammasome in vivo or in vitro. The results showed that methyl isoeugenol reduced cerebral infarct volume, modulated microglia M1/M2 phenotypes, and protected against NLRP3 inflammasome-primed Pyroptosis. Mechanistically, methyl isoeugenol increased the nuclear translocation of Nrf2 and decreased that of NF-κB, and consequently, upregulated cellular Antioxidants (HO-1 and NQO1), with the increased expression of antioxidant Enzymes SOD and the decreased expression of lipid peroxidation MDA. These findings suggest that Nrf2 may serve as a vital target for the protective effect of methyl isoeugenol, making methyl isoeugenol as a promising anti-neuroinflammatory agent for NLRP3 inflammasome mediated microglial neuroinflammation in I/R injury.

Keywords

Ischemia–reperfusion injury; Methyl isoeugenol; NLRP3 inflammasome; Nrf2; Pyroptosis.

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