Ophiocordyceps gracilioides is an entomoparasitic ascomycetes whose bioactivity has not been examined in detail. In this study, we identified the bioactive compounds ergosterol peroxide (EPO) and ergosterol (ERG) from the MeOH extract of O. gracilioides mycelia related to its anti-cancer effects by targeting the Nuclear Factor kappa B (NF-ĸB)/Signal Transducer and Activator of Transcription 3 (STAT3) inflammatory pathways. Using gene-reporter assays, we demonstrated that EPO markedly inhibits both NF-ĸB and STAT3 activity in 4T1 cells, whereas ERG had limited effect. Consistent with their effects on NF-ĸB and STAT3 activity, EPO, but not ERG, exerted anti-proliferative effects on 4T1 cells. Furthermore, EPO significant inhibited both the migration and invasion of 4T1 cells in vitro, and pre-treatment of 4T1 cells with EPO significantly inhibited the formation of experimental lung metastases in vivo. Collectively, we demonstrated that ERG and EPO can be isolated from O. gracilioides mycelia, and further identified EPO as an active constituent of its anti-metastatic effects through the inhibition of NF-ĸB and STAT3 inflammatory pathways in 4T1 breast cancer cells.

Ophiocordyceps gracilioides是一种昆虫寄生子囊菌，其生物活性尚未得到详细研究。在这项研究中，我们从O. gracilioides的 MeOH 提取物中鉴定了生物活性化合物过氧化麦角甾醇 (EPO) 和麦角甾醇 (ERG)菌丝体通过靶向核因子 kappa B (NF-ĸB)/信号转导器和转录激活因子 3 (STAT3) 炎症途径与其抗癌作用相关。使用基因报告分析，我们证明 EPO 显着抑制 4T1 细胞中的 NF-ĸB 和 STAT3 活性，而 ERG 的作用有限。与其对 NF-ĸB 和 STAT3 活性的影响一致，EPO 而不是 ERG，对 4T1 细胞产生抗增殖作用。此外，EPO在体外显着抑制4T1细胞的迁移和侵袭，用EPO预处理4T1细胞在体内显着抑制实验性肺转移的形成。总的来说，我们证明了 ERG 和 EPO 可以从O. gracilioides 中分离出来 菌丝体，并通过抑制 4T1 乳腺癌细胞中的 NF-ĸB 和 STAT3 炎症通路，进一步确定 EPO 是其抗转移作用的活性成分。