Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
College of Natural Sciences, Cantho University, Campus II, Cantho City 94000, Vietnam.
Biomolecules. 2020 May 4;10(5):711. doi: 10.3390/biom10050711.
was screened in an ongoing project to discover anti-influenza candidates from natural products. An extensive phytochemical investigation provided 26 compounds, including two new megastigmane glycosides ( and ), 21 diterpenoids (), and three flavonoids (). The chemical structures were elucidated by a series of chemical reactions, including modified Mosher's analysis and various spectroscopic measurements such as LC/MS and 1D- and 2D-NMR. The anti-influenza A activities of all isolates were screened by cytopathic effect (CPE) inhibition assays and neuraminidase (NA) inhibition assays. Ten candidates were selected, and detailed mechanistic studies were performed by various assays, such as Western blot, immunofluorescence, real-time PCR and flow cytometry. Compound exerted its antiviral activity not by direct neutralizing virion surface proteins, such as HA, but by inhibiting the expression of viral mRNA. In contrast, compound showed NA inhibitory activity in a noncompetitive manner with little effect on viral mRNA expression. Interestingly, both compounds and were shown to inhibit nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Taken together, these results provide not only the chemical profiling of but also anti-influenza A candidates.
在一项从天然产物中发现抗流感候选物的进行中项目中对其进行了筛选。广泛的植物化学研究提供了 26 种化合物，包括两种新的巨型倍半萜糖苷（和）、21 种二萜（）和三种类黄酮（）。通过一系列化学反应，包括改良的 Mosher 分析和各种光谱测量，如 LC/MS 和 1D-和 2D-NMR，阐明了化学结构。通过细胞病变效应（CPE）抑制试验和神经氨酸酶（NA）抑制试验筛选所有分离物的抗流感 A 活性。选择了 10 种候选物，并通过各种试验（如 Western blot、免疫荧光、实时 PCR 和流式细胞术）进行了详细的机制研究。化合物不是通过直接中和病毒表面蛋白（如 HA）发挥抗病毒活性，而是通过抑制病毒 mRNA 的表达。相比之下，化合物以非竞争性方式表现出 NA 抑制活性，对病毒 mRNA 表达的影响很小。有趣的是，两种化合物和都被证明以剂量依赖的方式抑制一氧化氮（NO）的产生和诱导型一氧化氮合酶（iNOS）的表达。总之，这些结果不仅提供了的化学特征，还提供了抗流感 A 候选物。
