Furuya Ayami, Uozaki Misao, Yamasaki Hisashi, Arakawa Tsutomu, Arita Mikio, Koyama A Hajime
Department of Cellular and Molecular Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
Int J Mol Med. 2008 Oct;22(4):541-5.
In the present study, ascorbic acid weakly inhibited the multiplication of viruses of three different families: herpes simplex virus type 1 (HSV-1), influenza virus type A and poliovirus type 1. Dehydroascorbic acid, an oxidized form of ascorbic acid and hence without reducing ability, showed much stronger antiviral activity than ascorbic acid, indicating that the antiviral activity of ascorbic acid is due to factors other than an antioxidant mechanism. Moreover, addition of 1 mM Fe3+, which oxidizes ascorbic acid to dehydroascorbic acid and also enhances the formation of hydroxyl radicals by ascorbic acid in the culture media, strongly enhanced the antiviral activity of ascorbic acid to a level significantly stronger than that of dehydroascorbic acid. Although both ascorbic acid and dehydroascorbic acid showed some cytotoxicity, the degree of cytotoxicity of the former was 10-fold higher than the latter, suggesting that the observed antiviral activity of ascorbic acid with and without ferric ion is, at least in part, a secondary result of the cytotoxic effect of the reagent, most likely due to the free radicals. However, the possibility that oxidation of ascorbic acid also contributed to the antiviral effects of ascorbic acid exists, in particular in the presence of ferric ion, since dehydroascorbic acid exhibited a very strong antiviral activity. Characterization of the mode of antiviral action of dehydroascorbic acid revealed that the addition of the reagent even at 11 h post infection almost completely inhibited the formation of progeny infectious virus in the infected cells, indicating that the reagent inhibits HSV-1 multiplication probably at the assembly process of progeny virus particles after the completion of viral DNA replication.
在本研究中，抗坏血酸对三种不同科的病毒增殖有微弱抑制作用：1型单纯疱疹病毒（HSV - 1）、甲型流感病毒和1型脊髓灰质炎病毒。脱氢抗坏血酸是抗坏血酸的氧化形式，因此没有还原能力，但其抗病毒活性比抗坏血酸强得多，这表明抗坏血酸的抗病毒活性并非源于抗氧化机制等因素。此外，添加1 mM Fe3 +可将抗坏血酸氧化为脱氢抗坏血酸，还能增强培养基中抗坏血酸产生羟基自由基的能力，从而显著增强抗坏血酸的抗病毒活性，使其抗病毒活性水平明显高于脱氢抗坏血酸。尽管抗坏血酸和脱氢抗坏血酸都表现出一定的细胞毒性，但前者的细胞毒性程度比后者高10倍，这表明观察到的抗坏血酸在有和没有铁离子情况下的抗病毒活性，至少部分是该试剂细胞毒性作用的次要结果，很可能是由于自由基导致的。然而，抗坏血酸的氧化也对抗坏血酸的抗病毒作用有贡献这种可能性是存在的，特别是在有铁离子存在的情况下，因为脱氢抗坏血酸表现出非常强的抗病毒活性。对脱氢抗坏血酸抗病毒作用模式的表征显示，即使在感染后11小时添加该试剂，也几乎完全抑制了感染细胞中子代感染性病毒的形成，这表明该试剂可能在病毒DNA复制完成后子代病毒颗粒的组装过程中抑制HSV - 1的增殖。
