{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:42:51Z","timestamp":1790476971883,"version":"4.1.0"},"reference-count":49,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Research Project","award":["201907835"],"award-info":[{"award-number":["201907835"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an <jats:italic>in vitro<\/jats:italic> model. The cerebral hypoxia injury cell model was produced by hypoxia\/reoxygenation (H\/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC\/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE84216\">GSE84216<\/jats:uri> retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H\/R-exposed neurons. Subsequently, through analyzing <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE84216\">GSE84216<\/jats:uri> from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H\/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4\/NF-\u03baB pathway, finally leading to the improvement of cell injury in H\/R-exposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in <jats:italic>in vitro<\/jats:italic> experiments through blocking activation of the TLR4\/NF-\u03baB signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury.<\/jats:p>","DOI":"10.7717\/peerj.13523","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T08:51:33Z","timestamp":1657875093000},"page":"e13523","source":"Crossref","is-referenced-by-count":15,"title":["Muscone improves hypoxia\/reoxygenation (H\/R)-induced neuronal injury by blocking HMGB1\/TLR4\/NF-\u03baB pathway <i>via<\/i> modulating 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