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In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein\/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-\u03baB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-\u03baB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-\u03baB\/NLRP3\/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-\u03baB, GSDMD-N, cleaved caspase-1, TNF-\u03b1, IL-6, and IL-1\u03b2, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-\u03baB\/NLRP3\/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.<\/jats:p>","DOI":"10.3390\/ijms241914771","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T16:57:06Z","timestamp":1696179426000},"page":"14771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-\u03baB\/NLRP3\/GSDMD Pathway"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-1241","authenticated-orcid":false,"given":"Pan","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuwei","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(23)00806-1","article-title":"The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): An international, stepped wedge cluster randomised controlled trial","volume":"402","author":"Ma","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1161\/STR.0000000000000407","article-title":"American Heart Association\/American Stroke, 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association\/American Stroke Association","volume":"53","author":"Greenberg","year":"2022","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107022","DOI":"10.1016\/j.isci.2023.107022","article-title":"Induced neural stem cells suppressed neuroinflammation by inhibiting the microglial pyroptotic pathway in intracerebral hemorrhage rats","volume":"26","author":"Liu","year":"2023","journal-title":"iScience"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s11910-023-01282-2","article-title":"Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke","volume":"23","author":"Alsbrook","year":"2023","journal-title":"Curr. 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