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Anti-influenza A virus mechanism of three representative compounds from Flos Trollii via TLRs signaling pathways.

金莲花 3 种代表性化合物通过 TLRs 信号通路的抗甲型流感病毒机制。

  • 影响因子:3.68
  • DOI:10.1016/j.jep.2020.112634
  • 作者列表:"Shi D","Chen M","Liu L","Wang Q","Liu S","Wang L","Wang R
  • 发表时间:2020-01-28
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:Flos Trollii is the dried flowers of Trollius chinensis. It has been used as a traditional herbal medicine for the treatment of upper respiratory tract infection, tonsillitis and pharyngitis in China for a long history. Veratric acid, vitexin, and trolline are the representative compounds of phenolic acids, flavonoids and alkaloids in this herbal medicine. All of these three compounds show antiviral activity which is related to the efficacy of Flos Trollii. AIM OF THE STUDY:To investigate the anti-influenza A virus mechanism of the three representative compounds from the perspective of regulating TLRs signaling pathways, so as to understand the relevant efficacy of Flos Trollii. MATERIALS AND METHODS:Influenza A virus A/FM/1/47 (H1N1) and mouse peritoneal macrophages (RAW264.7) were used in the whole process of investigation. MTT assay was conducted to select the appropriate experimental concentrations of the three compounds on RAW264.7 cells. Western blot, RT-PCR, and ELISA assays were performed to determine the protein and mRNA expression of key factors and related inflammatory factors of TLRs signaling pathways. Griess method was employed to detect the production of NO. RESULTS:The three representative compounds reduced the inflammatory factors including NO, IL-6, and TNF-α and enhanced the production of IFN-β through dynamically regulating the TLRs 3, 4 and 7 pathways. Veratric acid significantly down-regulated the protein expression of TLR3 and IRF3 as well as the mRNA expression of TBK1 and TRIF. Vitexin significantly down-regulated the protein expression of TBK1 and IRF3 as well as the mRNA expression of TLR3, TBK1, TRIF and IRF3 while up-regulated the protein expression of TLR4 and IKKα. Trolline significantly down-regulated the protein expression of TLR7 whereas significantly up-regulated the protein expression of TLR4, IKKα and TAK1. CONCLUSIONS:The three representative compounds from Flos Trollii play their parts in anti-H1N1 viral effect through partially down-regulating TLRs 3 and 7 pathways and up-regulating TLR4 pathway. They counteract the inflammatory injury caused by excessive production of NO, IL-1, IL-6, and TNF-α induced by virus infection and enhance the production of IFN-β so as to eliminate the virus.

摘要

民族药理学相关性: 金莲花是金莲花的干花。在我国作为治疗上呼吸道感染、扁桃体炎、咽炎的传统草药已有悠久的历史。苦味酸、牡荆素和特效酸是该草药中酚酸类、黄酮类和生物碱的代表化合物。这三个化合物均显示出与金莲花功效有关的抗病毒活性。 研究目的: 从调节 TLRs 信号通路的角度探讨 3 种代表性化合物抗甲型流感病毒的作用机制,以了解金莲花的相关功效。 材料与方法: 采用甲型流感病毒 A/FM/1/47 (H1N1) 和小鼠腹腔巨噬细胞 (RAW264.7) 进行全程调查。MTT 法选择 3 种化合物对 RAW264.7  细胞的适宜实验浓度。Western blot 、 RT-PCR 和 ELISA 检测 TLRs 信号通路关键因子和相关炎症因子的蛋白和 mRNA 表达。采用 Griess 法检测 NO 的产生。 结果: 3 个有代表性的化合物通过动态调节 TLRs 3 、 4 、 7 通路,降低 NO 、 IL-6 、 TNF-α 等炎症因子,增强 IFN-β 的产生。Vermide acid 显著下调 TLR3 和 IRF3 的蛋白表达以及 TBK1 和 TRIF 的 mRNA 表达。牡荆素显著下调 TBK1 和 IRF3 的蛋白表达以及 TLR3 、 TBK1 、 TRIF 和 IRF3 的 mRNA 表达,同时上调 TLR4 和 ikk α 的蛋白表达。Controlline 显著下调 TLR7 的蛋白表达,而显著上调 TLR4 、 ikk α 和 tak1 的蛋白表达。 结论: 金莲花中 3 个具有代表性的化合物通过部分下调 TLRs 3 和 7 通路,上调 TLR4 通路发挥 anti-H1N1 病毒作用。它们能对抗病毒感染引起的 NO 、 IL-1 、 IL-6 、 TNF-α 过度产生的炎性损伤,增强 IFN-β 的产生,从而清除病毒。

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影响因子:5.31
发表时间:2020-01-19
DOI:10.1093/cid/ciaa050
作者列表:["Baum U","Kulathinal S","Auranen K","Nohynek H"]

METHODS:BACKGROUND:From 2015/16 through 2017/18, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in two-year-olds was estimated for all three seasons. METHODS:Each season, a nationwide register-based cohort study was conducted. The study population comprised 60,088 children in 2015/16, 60,860 children in 2016/17 and 60,345 children in 2017/18. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS:From 2015/16 through 2017/18, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2%-69.0%), 20.3% (-12.7% to 43.6%) and 30.5% (10.9%-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9%-89.8%), 24.5% (-29.8% to 56.1%) and -20.1% (-61.5% to 10.7%). Neither of the influenza vaccines clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS:To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates expressing also overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

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影响因子:1.36
发表时间:2020-01-20
DOI:10.1111/1348-0421.12775
作者列表:["Ainai A","van Riet E","Ito R","Ikeda K","Senchi K","Suzuki T","Tamura SI","Asanuma H","Odagiri T","Tashiro M","Kurata T","Multihartina P","Setiawaty V","Andriana Pangesti KN","Hasegawa H"]

METHODS::Intranasally administered influenza vaccines could be more effective than injected vaccines, since intranasal vaccination can induce virus-specific IgA antibodies in the upper respiratory tract, which is the initial site of infection. In the current study, immune responses elicited by an intranasal inactivated H5 influenza vaccine were evaluated in healthy H5 influenza virus-naive individuals. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy-vinyl polymer (CVP), had a notable impact on the induction of nasal IgA antibody responses but not serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific helper T (Th) cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against H5 influenza viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses. This article is protected by copyright. All rights reserved.

影响因子:6.53
发表时间:2020-01-21
DOI:10.1016/S1473-3099(19)30584-5
作者列表:["Liebowitz D","Gottlieb K","Kolhatkar NS","Garg SJ","Asher JM","Nazareno J","Kim K","McIIwain DR","Tucker SN"]

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