Huina Liu , Weitao Chen , Meiyuan He , Linlin Nie , Yaru Pan , Danni Guan , Yongyi Li , Ting Wan , Lining Duan , Cong Yang , Weirong Li , Qi wang , Lixing Zhuang , Yifan Zhang
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引用次数: 0
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.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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