Yokochi S, Ishiwata Y, Saito H, Ebinuma H, Tsuchiya M, Ishii H
Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
Arzneimittelforschung. 1997 Aug;47(8):968-74.
The liver extract preparation Adelavin9 (referred to as EXT-FAD hereinafter) is a combination product that consists of hog liver extract and flavin-adenine dinucleotide (FAD). EXT-FAD has been reported to improve the histology of chronic liver injury and is widely used in Japan. Interferon (IFN) has been used to treat viral hepatitis. In this study, the action of EXT-FAD on the antiviral activity of IFN was examined using experimental models of viral infection in vitro and in vivo. EXT-FAD significantly enhanced the 2',5'-oligoadenylate synthetase (2-5AS) activity in human peripheral blood mononuclear cells (PBMC) treated with human IFN-alpha-2a. EXT-FAD is likely to affect the late phase of IFN action to produce the antiviral activity. Combination of IFN-alpha-2a with EXT-FAD produced a synergistic inhibitory effect against herpes simplex virus type-1 (HSV-1) in vitro. The effect of EXT-FAD in combination with IFN-alpha-2a against influenza virus type A (Fluv A) was also examined and a similar effect to that found in the anti-HSV-1 assay was observed. In addition, administration of EXT-FAD to mice infected with HSV-1 significantly prolonged the mean survival periods. The intracellular redox state plays a role in inhibiting virus replication. EXT-FAD was found to increase the intracellular glutathione (GSH) level. EXT-FAD also enhanced the nitric oxide synthase (NOS) activity, which plays a role in antiviral effects. This result indicate that the effect of EXT-FAD on the antiviral activity of IFN is partially related to increased intracellular GSH levels and NOS activation.
肝提取物制剂Adelavin9（以下简称EXT-FAD）是一种由猪肝提取物和黄素腺嘌呤二核苷酸（FAD）组成的复合产品。据报道，EXT-FAD可改善慢性肝损伤的组织学表现，在日本被广泛使用。干扰素（IFN）已被用于治疗病毒性肝炎。在本研究中，使用体外和体内病毒感染实验模型研究了EXT-FAD对IFN抗病毒活性的作用。EXT-FAD显著增强了用人干扰素α-2a处理的人外周血单个核细胞（PBMC）中的2',5'-寡腺苷酸合成酶（2-5AS）活性。EXT-FAD可能影响IFN作用的后期以产生抗病毒活性。干扰素α-2a与EXT-FAD联合使用在体外对单纯疱疹病毒1型（HSV-1）产生了协同抑制作用。还研究了EXT-FAD与干扰素α-2a联合使用对甲型流感病毒（Fluv A）的作用，观察到与抗HSV-1试验中发现的类似效果。此外，给感染HSV-1的小鼠施用EXT-FAD可显著延长平均生存期。细胞内氧化还原状态在抑制病毒复制中起作用。发现EXT-FAD可提高细胞内谷胱甘肽（GSH）水平。EXT-FAD还增强了一氧化氮合酶（NOS）的活性，该酶在抗病毒作用中起作用。这一结果表明，EXT-FAD对IFN抗病毒活性的影响部分与细胞内GSH水平升高和NOS激活有关。
