摘要
【Background】 Chikusetsusaponin IVa (CHS) is a triterpenoid saponin that has been demonstrated to possess multiple properties. 【Purpose】 This study focused on inhibiting H9N2 avian influenza virus (AIV) by CHS and investigated the underlying mechanisms, specifically targeting the nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway. 【Methods】 The antiviral activity of CHS was evaluated by determining its half inhibitory concentration and therapeutic index (TI) in vitro. Markers of oxidative stress, encompassing superoxide dismutase, glutathione peroxidase, and malondialdehyde levels, were assessed. Analyses of pathways from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were conducted to elucidate the underlying mechanisms, followed by network investigation and simulations of molecular docking. Moreover, the effects of CHS on Nrf2 and mitogen-activated protein kinase (MAPK) signaling pathways were assessed in human lung carcinoma A549 cells and a mouse model of H9N2 AIV infection. 【Results】 CHS showed inhibitory effects on H9N2 AIV in vitro, with TI values of 4.00 (co-treatment) and 6.29 (posttreatment). CHS reduced H9N2 AIV-induced oxidative stress and was predicted to target Nrf2, MAPK/phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways, and oxidation–reduction processes. Molecular docking analysis revealed a high affinity between CHS and Nrf2. In A549 cells, CHS enhanced Nrf2 activation, inhibited MAPK signaling, and reduced H9N2 AIV-induced oxidative stress. The therapeutic mechanism of CHS was found to be mediated by Nrf2. In a mouse model, CHS mitigated pulmonary impairment, improving the organism’s antioxidant activity. CHS also regulated the Nrf2 and MAPK signaling pathways in lung tissue. 【Conclusion】 CHS inhibits H9N2 AIV and alleviates virus-induced oxidative stress by targeting the Nrf2 signaling pathway. These observations lay the groundwork for devising prospective therapeutic interventions targeting H9N2 AIV infection.
摘要译文
【背景】chikusetsusaponin IVA（CHS）是一种三萜皂苷，已被证明具有多种特性。【目的】目的是该研究的重点是CHS抑制H9N2鸟类流感病毒（AIV）并研究了潜在机制，特别针对核因子红细胞相关因子2（NRF2）信号通路。【方法】通过确定体外确定其一半抑制浓度和治疗指数（Ti）的一半抑制浓度和治疗指数（TI）的抗病毒活性。评估了氧化应激的标志物，包括超氧化物歧化酶，谷胱甘肽过氧化物酶和丙二醛水平。对基因，基因组和基因本体学百科全书的途径进行分析以阐明基本机制，然后进行网络研究和分子对接的模拟。此外，在人类肺A549细胞和H9N2 AIV感染的小鼠模型中评估了CHS对NRF2和有丝分裂原激活蛋白激酶（MAPK）信号通路的影响。【结果】CHS在体外显示对H9N2 AIV的抑制作用，Ti值为4.00（共处理）和6.29（处理后）。CHS降低了H9N2 AIV诱导的氧化应激，并被预测为NRF2，MAPK/磷酸肌醇3-激酶（PI3K） - 蛋白酶激酶B（AKT）信号传导途径和氧化 - 还原过程。分子对接分析显示CHS和NRF2之间具有高亲和力。在A549细胞中，CHS增强了NRF2激活，抑制了MAPK信号，并减少了H9N2 AIV诱导的氧化应激。发现CHS的治疗机制是由NRF2介导的。在小鼠模型中，CHS减轻肺部损伤，改善了生物体的抗氧化活性。CHS还调节肺组织中的NRF2和MAPK信号通路。【结论】CHS抑制H9N2 AIV，并通过靶向NRF2信号通路来减轻病毒诱导的氧化应激。这些观察结果是设计针对H9N2 AIV感染的前瞻性治疗干预措施的基础。
Qi Dai [1];Song-Tao Wu [2];Xin Zheng [3];Peng-Tao You [4];Yan-Wen Liu [5];Yuan Zhao [6];Xiu-Qiao Zhang (0000-0003-4545-3284) [7];. Chikusetsusaponin IVa Targets Nrf2 to Inhibit H9N2 Avian Influenza Virus Infection[J]. Pharmacognosy Magazine, 2025,21(2): 584–598