Hanada Akari, Morimoto Ryosuke, Horio Yuka, Shichiri Mototada, Nakashima Ayaka, Ogawa Taro, Suzuki Kengo, Sumitani Hidenobu, Ogata Tokutaro, Isegawa Yuji
Department of Food Sciences and Nutrition Mukogawa Women's University Nishinomiya Japan.
Present address: Faculty of Human Life Science Shikoku University Tokushima Japan.
Food Sci Nutr. 2022 Jan 23;10(3):926-935. doi: 10.1002/fsn3.2725. eCollection 2022 Mar.
We previously demonstrated the anti-influenza activity of var. (wild watermelon, WWM); however, the active ingredient was unknown. Here, we performed metabolomic analysis to evaluate the ingredients of WWM associated with antiviral activity. Many low-molecular weight compounds were identified, with flavonoids accounting for 35% of all the compounds in WWM juice. Prenylated flavonoids accounted for 30% of the flavonoids. Among the measurable components of phytoestrogens in WWM juice, 8-prenylnaringenin showed the highest antiviral activity. We synthesized 8-prenylnaringenin and used liquid chromatography-mass spectrometry to quantitate the active ingredient in WWM. The antiviral activities of 8-prenylnaringenin were observed against H1N1 and H3N2 influenza A subtypes and influenza B viruses. Moreover, 8-prenylnaringenin was found to inhibit virus adsorption and late-stage virus replication, suggesting that the mechanisms of action of 8-prenylnaringenin may differ from those of amantadine and oseltamivir. We confirmed that 8-prenylnaringenin strongly inhibited the viral entry of all the influenza virus strains that were examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. This result indicates that 8-prenylnaringenin may activate the host cell's defense mechanisms, rather than directly acting on the influenza virus. Since 8-prenylnaringenin did not inhibit late-stage virus replication of oseltamivir-resistant strains, 8-prenylnaringenin may interact directly with viral neuraminidase. These results are the first report on the anti-influenza virus activity of 8-prenylnaringenin. Our results highlight the potential of WWM and phytoestrogens to develop effective prophylactic and therapeutic approaches to the influenza virus.
我们之前证明了西瓜变种（野生西瓜，WWM）的抗流感活性；然而，其活性成分尚不清楚。在此，我们进行了代谢组学分析，以评估与抗病毒活性相关的WWM成分。鉴定出了许多低分子量化合物，其中黄酮类化合物占WWM果汁中所有化合物的35%。异戊烯基黄酮占黄酮类化合物的30%。在WWM果汁中可测量的植物雌激素成分中，8-异戊烯基柚皮素表现出最高的抗病毒活性。我们合成了8-异戊烯基柚皮素，并使用液相色谱-质谱法对WWM中的活性成分进行定量。观察到8-异戊烯基柚皮素对甲型H1N1和H3N2流感亚型病毒以及乙型流感病毒具有抗病毒活性。此外，发现8-异戊烯基柚皮素可抑制病毒吸附和后期病毒复制，这表明8-异戊烯基柚皮素的作用机制可能与金刚烷胺和奥司他韦不同。我们证实，8-异戊烯基柚皮素强烈抑制了所有检测的流感病毒株的病毒进入，包括那些对抗流感药物奥司他韦和金刚烷胺耐药的病毒株。这一结果表明，8-异戊烯基柚皮素可能激活宿主细胞的防御机制，而不是直接作用于流感病毒。由于8-异戊烯基柚皮素不抑制奥司他韦耐药株的后期病毒复制，8-异戊烯基柚皮素可能直接与病毒神经氨酸酶相互作用。这些结果是关于8-异戊烯基柚皮素抗流感病毒活性的首次报道。我们的结果突出了WWM和植物雌激素在开发针对流感病毒的有效预防和治疗方法方面的潜力。
