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来自皱盖拟小牛肝菌子实体的 Sarcodonol A-D 抑制 MRC-5 细胞中 HCoV-OC43 诱导的细胞凋亡。

Sarcodonol A-D from fruiting bodies of Sarcodon imbricatus inhibits HCoV-OC43 induced apoptosis in MRC-5 cells.

机构信息

Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea; College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.

Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea.

出版信息

Bioorg Chem. 2023 Nov;140:106824. doi: 10.1016/j.bioorg.2023.106824. Epub 2023 Sep 1.

Abstract

Four new 26-carboxylated ergostane-type sterols (Sarcodonol A-D) were isolated from 70% ethanol extracts of dried fruiting bodies of Sarcodon imbricatus. Their chemical structures were elucidated using 1D- and 2D-nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and confirmed by comparison with previously reported data. As far as we know, this is the first instance of isolating a 26-carboxylated ergostane-type sterol from nature. The determined antiviral efficacy of sarcodonol A-D (1-4) against HCoV-OC43 in MRC-5 cells confirmed that sarcodonol D (4) had significant antiviral activity. Notably, sarcodonol D (4) potently blocked virus infection at low-micromolar concentration and showed high SI (IC = 2.26 μM; CC > 100 μM; SI > 44.2). In addition, this research shows that the antiviral effect of sarcodonol D (4) via reduced apoptosis increased by viral infection is through mitochondrial stress regulation. This suggests that sarcodonol D (4) is a potential candidate for use as an antiviral treatment.

摘要

从皱边网柄牛肝菌(Sarcodon imbricatus)干子实体的 70%乙醇提取物中分离得到四个新的 26-羧基麦角甾烷型甾醇(Sarcodonol A-D)。通过一维和二维核磁共振和高分辨率电喷雾电离质谱法阐明了它们的化学结构,并通过与以前报道的数据进行比较得到了证实。据我们所知,这是首次从自然界中分离出 26-羧基麦角甾烷型甾醇。Sarcodonol A-D(1-4)对 MRC-5 细胞中的 HCoV-OC43 的抗病毒功效的确定表明,Sarcodonol D(4)具有显著的抗病毒活性。值得注意的是,Sarcodonol D(4)以低微摩尔浓度强效阻断病毒感染,且具有高 SI(IC=2.26 μM;CC>100 μM;SI>44.2)。此外,本研究表明,通过感染病毒增加的凋亡减少来调节线粒体应激,Sarcodonol D(4)发挥抗病毒作用。这表明 Sarcodonol D(4)是一种有潜力的抗病毒治疗候选药物。

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