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In this study, we probed the prospective protective influence of melittin on cerebral ischemia, focusing on its anti-inflammatory activity. Mechanistically, we explored whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as ZC3H12A), a recently identified zinc-finger protein, played a role in melittin-mediated anti-inflammation and neuroprotection. Male C57\/BL6 mice were subjected to distal middle cerebral artery occlusion to create a focal cerebral cortical ischemia model, with melittin administered intraperitoneally. We evaluated motor functions, brain infarct volume, cerebral blood flow, and inflammatory marker levels within brain tissue, employing quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and western blotting. In vitro, an immortalized BV-2 microglia culture was stimulated with lipopolysaccharide (LPS) to establish an inflammatory cell model. Post-melittin exposure, cell viability, and cytokine expression were examined. MCPIP1 was silenced using siRNA in LPS-induced BV-2 cells, with the ensuing nuclear translocation of nuclear factor-\u03baB assessed through cellular immunofluorescence. In vivo, melittin enhanced motor functions, diminished infarction, fostered blood flow restoration in ischemic brain regions, and markedly inhibited the expression of inflammatory cytokines (interleukin-1\u03b2, interleukin-6, tumor necrosis factor-\u03b1, and nuclear factor-\u03baB). In vitro, melittin augmented MCPIP1 expression in LPS-induced BV-2 cells and ameliorated inflammation-induced cell death. The neuroprotective effect conferred by melittin was attenuated upon MCPIP1 knockdown. Our findings establish that melittin-induced tolerance to ischemic injury is intrinsically linked with its anti-inflammatory capacity. Moreover, MCPIP1 is, at the very least, partially implicated in this process.<\/jats:p>","DOI":"10.1007\/s11064-023-04030-7","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T15:01:46Z","timestamp":1696863706000},"page":"348-362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neuroprotective Effects of Melittin Against Cerebral Ischemia and Inflammatory Injury via Upregulation of MCPIP1 to Suppress NF-\u03baB Activation In Vivo and In Vitro"],"prefix":"10.1007","volume":"49","author":[{"given":"Xing","family":"Xing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruisheng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"issue":"3","key":"4030_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3390\/toxins13030191","volume":"13","author":"W Kim","year":"2021","unstructured":"Kim W (2021) Bee Venom and its sub-components: characterization, pharmacology, and therapeutics. 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