Yang Guanyu, Qin Mengwei, Chen Mingbin, Shi Yujia, Liu Siyi, Rao Yong, Huang Ling, Fu Ying
Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
Mar Drugs. 2025 Feb 20;23(3):94. doi: 10.3390/md23030094.
Three new eremophilane sesquiterpenoids (-), together with six known analogues, were isolated from the marine-derived fungus sp. DXH009. Their structures were elucidated through detailed NMR and MS spectroscopic analysis, and the absolute configurations of - 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 (dihydrosporogen AO-1) exhibited significant inhibitory effects on the production of nitric oxide (NO) levels (EC = 3.11 μM) 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-κB pathway as well as the expression levels of key neuroinflammatory markers, including COX2, TNF-α, IL-6, and IL-1β. Correspondingly, treating in LPS-induced mice efficiently ameliorated neuroinflammation in the tissues of the cortex and hippocampus. These findings suggest that eremophilane sesquiterpenoid could be a potential candidate for the development of anti-neuroinflammatory drugs.
从海洋来源的真菌sp. DXH009中分离出了三种新的桉烷倍半萜类化合物（-），以及六种已知类似物。通过详细的核磁共振（NMR）和质谱（MS）光谱分析阐明了它们的结构，并通过构象分析和量子化学TDDFT-ECD计算确定了-的绝对构型。使用脂多糖（LPS）诱导的BV2小胶质细胞评估了它们的抗神经炎症活性。结果表明，化合物（二氢孢子原AO-1）对一氧化氮（NO）水平的产生表现出显著的抑制作用（EC = 3.11 μM），细胞毒性较小，导致LPS处理的BV2小胶质细胞中诱导巨噬细胞极化的逆转效应。这些与经典NF-κB途径的抑制以及关键神经炎症标志物COX2、TNF-α、IL-6和IL-1β的表达水平相关。相应地，在LPS诱导的小鼠中使用进行治疗可有效改善皮质和海马组织中的神经炎症。这些发现表明，桉烷倍半萜类化合物可能是开发抗神经炎症药物的潜在候选物。
