{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:20:16Z","timestamp":1783653616683,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Due to the anti-inflammatory and antioxidant properties of cynaroside (Cyn), it may be useful in the treatment of cerebral ischemia\/reperfusion injury (I\/R). This study aims to evaluate the effect of Cyn on cerebral ischemia\/reperfusion injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transient middle cerebral artery occlusion model (tMCAO) and oxygen and glucose deprivation\/reperfusion (OGD\/R) microglia models were used to evaluate the effect of Cyn. The direct interaction between Cyn and Alox15 was investigated through bioinformatics, molecular docking and biolayer interferometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>tMCAO mice treated with Cyn show improved neurological deficits, reduced infarct volume and edema, and inhibition of microglial activation. In addition, Cyn inhibited tMCAO-induced Alox15 expression. Cyn significantly reduced the overproduction of the M1 microglia-regulated pro-inflammatory cytokines NLRP3, ASC, and cleaved caspase-1, as well as the overproduction of IL-1\u03b2 and IL-18, induced by tMCAO or OGD\/R. Cyn also inhibits the expression of Tfrc, COX2, and Acsl4 in tMCAO and OGD\/R-treated mice and BV-2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results suggest that Cyn may attenuate cerebral ischemia\/reperfusion injury by inhibiting Alox15 to reduce inflammation and reduce ferroptosis. This study reveals the underlying molecular mechanism of Cyn in the treatment of ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1490640","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:11:32Z","timestamp":1739509892000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cynaroside: a potential therapeutic agent targeting arachidonate 15-lipoxygenase to mitigate cerebral ischemia\/reperfusion 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