Michaelis Martin, Sithisarn Patchima, Cinatl Jindrich
Institute for Medical Virology, Clinics of the Goethe-University, Paul Ehrlich-Str, 40, 60596 Frankfurt am Main, Germany.
BMC Res Notes. 2014 Jun 23;7:384. doi: 10.1186/1756-0500-7-384.
Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.
Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.
These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.
已知不同的类黄酮会干扰甲型流感病毒的复制。最近，我们发现结构相似的类黄酮黄芩素和染料木黄酮通过不同机制抑制A549肺细胞中高致病性禽流感H5N1甲型流感病毒的复制。在此，我们研究了这两种化合物对H5N1诱导的活性氧（ROS）形成的影响以及ROS形成在H5N1复制过程中的作用。
黄芩素和染料木黄酮增强了A549细胞和原代人单核细胞衍生巨噬细胞中H5N1诱导的ROS形成。使用抗氧化剂N-乙酰-L-半胱氨酸抑制黄芩素和染料木黄酮诱导的ROS形成，强烈增强了这两种化合物在A549细胞中的抗H5N1活性，但在巨噬细胞中则不然。
这些发现强调类黄酮会诱导复杂的药理作用，其中一些可能干扰H5N1复制，而另一些可能支持H5N1复制。需要更详细地了解这些作用及其潜在的构效关系，以设计出具有优化抗H5N1活性的药物。
