University of Texas Health Science Center at Houston, Houston, TX, USA.
Phytomedicine. 2010 Nov;17(13):1047-56. doi: 10.1016/j.phymed.2010.03.016.
The emergence of resistance to anti-influenza drugs calls for the search for new antiviral molecules with different resistance profiles. Polyphenolic compounds are found in various plants and have antiviral and antioxidative properties. We tested the hypothesis that oligonol, a lychee fruit-derived low molecular weight polyphenol, possesses anti-influenza effects by inhibiting phosphorylation of extracellular-signal-regulated kinases (ERK). Real time PCR, plaque assay, and immunofluorescence techniques were used to study the effects of oligonol on proliferation of influenza virus. Oligonol inhibits influenza virus proliferation by blocking attachment of the virus to MDCK cells and by suppression of nuclear export of influenza virus ribonucleoprotein (RNP). Infection of MDCK cells with influenza virus leads to an increase in production of reactive oxygen species (ROS) and induction of a ROS-dependent ERK phosphorylation. Inhibition of ERK activation by a dominant negative mutant of ERK or N-acetyl-cysteine (NAC) leads to inhibition of influenza RNP nuclear export. Phorbol 12-myristate 13-acetate (PMA) induces ROS production, ERK phosphorylation and enhances influenza proliferation in MDCK cells. Oligonol and NAC inhibit PMA-induced ERK phosphorylation and ROS production. Our studies suggest that the underlying mechanism for the inhibitory effect of oligonol on influenza virus RNP nuclear export is blocking of ROS-dependent induction of ERK phosphorylation.
多酚化合物存在于各种植物中，具有抗病毒和抗氧化特性。我们通过检测荔枝果低分子量多酚寡诺醇通过抑制细胞外信号调节激酶（ERK）磷酸化来抑制流感病毒增殖的假说。实时 PCR、噬斑试验和免疫荧光技术用于研究寡诺醇对流感病毒增殖的影响。寡诺醇通过阻止病毒与 MDCK 细胞的附着以及抑制流感病毒核糖核蛋白（RNP）的核输出来抑制流感病毒的增殖。流感病毒感染 MDCK 细胞会导致活性氧（ROS）的产生增加，并诱导 ROS 依赖性 ERK 磷酸化。通过 ERK 的显性负突变体或 N-乙酰半胱氨酸（NAC）抑制 ERK 激活会导致流感 RNP 核输出抑制。佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导 ROS 产生、ERK 磷酸化并增强 MDCK 细胞中的流感增殖。寡诺醇和 NAC 抑制 PMA 诱导的 ERK 磷酸化和 ROS 产生。我们的研究表明，寡诺醇抑制流感病毒 RNP 核输出的作用机制是阻断 ROS 依赖性 ERK 磷酸化的诱导。
