{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:57:36Z","timestamp":1781672256144,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke is a common and severe cerebrovascular disease with high mortality and disability. Accumulating evidence indicates that \u03b2-caryophyllene (BCP) exerts neuroprotective effects against cerebral ischemic injury; however, the precise underlying mechanisms remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Focal cerebral ischemia\/reperfusion (I\/R) mouse models were established\n                      <jats:italic>in vivo<\/jats:italic>\n                      and oxygen-glucose deprivation\/reoxygenation (OGD\/R) was conducted in BV2 microglial cells and primary microglia\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated that BCP administration significantly reduced cerebral infarct volume, alleviated neurological deficits, and enhanced motor function in mice subjected to transient focal cerebral ischemia. Mechanistically, BCP inhibited pyroptosis and glycolysis in the ischemic penumbra of mice and in BV2 cells following OGD\/R. Concomitantly, BCP decreased the levels of H3K9 lactylation (H3K9la) and H3K18 lactylation (H3K18la) in brain tissues of ischemic penumbra and in OGD\/R-induced BV2 cells. Notably, co-treatment with lactate attenuated these inhibitory effects and abrogated the neuroprotective efficacy of BCP. Similar results were also obtained in primary microglia. Additionnaly, oxamate (the LDHA inhibitor) simultaneously downregulated the protein levels of H3K9la, H3K18la, and pyroptosis-related factors, while MCC950 (the NLRP3 inflammasome inhibitor) only blocked downstream pyroptosis without affecting histone lactylation. Chip-PCR further demonstrated that OGD\/R increased the enrichment of H3K9la and H3K18la at the NLRP3 promoter, which was decreased by BCP and oxamate but not by MCC950. Lactate supplementation partially restored the inhibitory effects of BCP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BCP protects against ischemic stroke by targeting the lactate-histone lactylation-pyroptosis axis, providing a potential therapeutic target for cerebral ischemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1840441","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:46:45Z","timestamp":1781671605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-Caryophyllene protects against ischemic stroke by inhibiting H3K9 and H3K18 lactylation-mediated cellular pyroptosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Qing","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Physiology, and Institute of Brain Science and Diseases, School of Basic Medicine, Qingdao University","place":["Qingdao, China"]},{"name":"Department of Physiology, Jining Medical University","place":["Jining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Jining NO.1 People\u2019s Hospital","place":["Jining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, and Institute of Brain Science and Diseases, School of Basic Medicine, Qingdao University","place":["Qingdao, China"]},{"name":"Department of Pharmacology, Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"110118","DOI":"10.1016\/j.jnutbio.2025.110118","article-title":"Dietary selenium deficiency activates the NLRP3 inflammasome to induce gallbladder pyroptosis by regulating glycolysis and histone lactylation through ROS\/HIF-1\u03b1 pathway","volume":"147","author":"An","year":"2026","journal-title":"J. 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