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DXH009. Their structures were elucidated through detailed NMR and MS spectroscopic analysis, and the absolute configurations of 1\u20134 were determined by conformational analysis and quantum chemical TDDFT-ECD calculation. Their anti-neuroinflammatory activities were evaluated using the lipopolysaccharide (LPS)-induced BV2 microglial cells. The results indicated that compound 5 (dihydrosporogen AO-1) exhibited significant inhibitory effects on the production of nitric oxide (NO) levels (EC50 = 3.11 \u03bcM) with less cytotoxicity, leading to a reversal effect in inducing microphage polarization in LPS-treated BV2 microglial cells. These were correlated with suppressions of the canonical NF-\u03baB pathway as well as the expression levels of key neuroinflammatory markers, including COX2, TNF-\u03b1, IL-6, and IL-1\u03b2. Correspondingly, treating 5 in LPS-induced mice efficiently ameliorated neuroinflammation in the tissues of the cortex and hippocampus. These findings suggest that eremophilane sesquiterpenoid 5 could be a potential candidate for the development of anti-neuroinflammatory drugs.<\/jats:p>","DOI":"10.3390\/md23030094","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:53:06Z","timestamp":1740124386000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Anti-Neuroinflammatory Eremophilane Sesquiterpenoids from Marine-Derived Fungus Phoma sp. DXH009"],"prefix":"10.3390","volume":"23","author":[{"given":"Guanyu","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengwei","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingbin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Rao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/glia.23571","article-title":"Neuroinflammation in the central nervous system: Symphony of glial cells","volume":"67","author":"Yang","year":"2019","journal-title":"Glia"},{"key":"ref_2","first-page":"9999146","article-title":"Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease","volume":"2021","author":"Udovin","year":"2021","journal-title":"Mediat. 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