The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, Iowa, United States of America ; Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, Iowa, United States of America ; Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, United States of America.
PLoS One. 2013 Sep 30;8(9):e76491. doi: 10.1371/journal.pone.0076491. eCollection 2013.
Hypericumperforatum (H. perforatum) ethanol extract has been found to inhibit lipopolysaccharide-induced production of inflammatory mediators and cytokines in cultured macrophages. Therefore, it may be able to protect the host from excessive inflammation during viral infection. In the current study, the immune-regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells, the extract (30 µg/mL) significantly inhibited influenza virus induced monocyte chemotactic protein (MCP)-1 and interferon-γ induced protein 10 kD (IP-10), but dramatically increased interleukin-6 (IL-6). In mice inoculated intranasally with 10(7.9) EID50 of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung viral titer, bronchoalveolar lavage (BAL) pro-inflammatory cytokine and chemokine levels, and the infiltration of pro-inflammatory cells in the lung 5 days post-inoculation, as compared to ethanol vehicle treated mice. Transcription of suppressor of cytokine signaling 3 (SOCS3) was increased by H. perforatum extract both in A549 cells and BALB/c mice, which could have interrupted anti-viral immune response and thus led to the inefficient viral clearance and increased lung inflammation. H. perforatum treatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10(5.0) EID50) and H. perforatum was applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10(7.9) EID50) suffered from a higher mortality rate when dosed with H. perforatum extract. In conclusion, the current study showed that SOCS3 elevation by H. perforatum may cause impaired immune defense against influenza virus infection and lead to higher mortality.
贯叶金丝桃（Hypericum perforatum）乙醇提取物已被发现可抑制培养的巨噬细胞中脂多糖诱导的炎症介质和细胞因子的产生。因此，它可能能够保护宿主在病毒感染期间免受过度炎症的影响。在本研究中，评估了贯叶金丝桃提取物在暴露于甲型流感病毒/PR/8/34 H1N1 的 A549 肺上皮细胞和 BALB/c 小鼠中的免疫调节作用。在 A549 细胞中，该提取物（30μg/mL）显著抑制流感病毒诱导的单核细胞趋化蛋白（MCP）-1 和干扰素-γ诱导的蛋白 10 kD（IP-10），但显著增加白细胞介素-6（IL-6）。在接种 10（7.9）EID50 的甲型流感病毒/PR/8/34 H1N1（高剂量）的小鼠中，每天口服贯叶金丝桃提取物（110mg/kg 体重），与乙醇载体处理的小鼠相比，在接种后 5 天增加了肺病毒滴度、支气管肺泡灌洗液（BAL）促炎细胞因子和趋化因子水平以及肺中促炎细胞的浸润。贯叶金丝桃提取物在 A549 细胞和 BALB/c 小鼠中均增加了细胞因子信号转导抑制因子 3（SOCS3）的转录，这可能中断了抗病毒免疫反应，从而导致病毒清除效率降低和肺部炎症增加。当用较低剂量（~10（5.0）EID50）接种小鼠且贯叶金丝桃在感染后期应用时，贯叶金丝桃处理导致病毒滴度略有降低而不影响体重。用高剂量流感病毒（10（7.9）EID50）鼻内攻击的小鼠用贯叶金丝桃提取物给药时，死亡率更高。总之，本研究表明，贯叶金丝桃引起的 SOCS3 升高可能导致对流感病毒感染的免疫防御受损，并导致更高的死亡率。
