王進崑WANG, CHIN-KUN陳柏愷CHEN, BO-KAIBO-KAICHEN營養學系博士班2026-02-102025-07-2920252025-07-10https://handle.ncl.edu.tw/11296/7hgeyuhttps://scholars.csmu.edu.tw/handle/123456789/5362呼吸道感染病毒,尤其是COVID-19造成全球大流行,創新且快速的治療策略迫切需求。雖然疫苗和抗病毒藥物在抑制疾病傳播和嚴重程度方面發揮了重要作用,營養策略是一個有希望且有潛力的領域。 本研究第一部分探討紫錐菊(Echinacea purpurea extracts;EPE)和靈芝萃取物(Ganoderma lucidum extracts;GE)及其混合物(Advanced G. lucidum drink; AG)對A型/B型流感病毒感染的抑制作用。確認GE和EPE是否增強細胞免疫以防止病毒感染或直接抑制病毒。本研究採用了細胞存活試驗和血球凝集試驗(Hemagglutination assay;HA assay)。利用不同樣品處理並與A/B型流感病毒共同培養細胞,AG、EPE及GE均可以提升細胞對抗病毒存活的能力。在HA試驗中,GE和EPE對A/B型流感病毒具有良好的抑制作用。所有樣品均具有改善因A/B型流感後導致的粒線體膜電位變化。GE和EPE能夠透過改善細胞存活率和粒線體功能障礙達到預防感染之功效,EPE可以直接抑制病毒並且是預防流感病毒感染之有效營養策略。 新型冠狀病毒(SARS-CoV-2)引起的大流行使世界陷入了發病率和死亡率極高的重大危機,並出現了各種變異病毒株。從SARS-CoV-2中康復的患者會發展為COVID-19急性期後的綜合症狀(長新冠),持續時間超過 12 週甚至更長,該機制尚未明確。基於COVID-19偽病毒一次性感染後失活的特性,本研究使用COVID-19偽病毒作為細胞感染COVID-19病毒之模型來觀察感染後,在移除病毒後所導致的細胞內急性變化。本研究使用ACE2-293T細胞作為感染COVID-19偽病毒的載體,細胞感染偽病毒後並移除偽病毒液,發現大量的亞鐵離子積聚在粒線體中,並進而釋放至細胞質中,造成大量的活性氧(ROS)堆積,致使粒線體功能受損。為評估營養策略對亞鐵離子蓄積和粒線體功能障礙的改善效果,本研究使用乳鐵蛋白、Co Q10 及EPE。結果顯示,乳鐵蛋白、Co Q10和EPE皆可以透過減少粒線體中亞鐵離子和ROS的堆積,進而改善粒線體功能受損。HPLC分析結果顯示,EPE含有豐富的咖啡酸,對粒線體功能障礙也有很好的改善效果。綜合上述,COVID-19偽病毒感染之細胞,即便病毒消失後,仍會增加粒線體內亞鐵離子和ROS的積累,並釋放到細胞質中,進一步導致粒線體功能之受損,可能進一步導致各種長新冠的症狀。以乳鐵蛋白、Co Q10和EPE作為營養策略,能有效降低粒線體內亞鐵離子及ROS之堆積,改善粒線體功能之受損。COVID-19 has spread worldwide since 2019. Respiratory viral infectious diseases such as influenza and respiratory syncytial virus (RSV) infection are also prevalent at the same time. Although vaccines and antiviral drugs are available for the prevention and treatment of diseases, nutritional strategy could be an alternative option. This study investigated the inhibitory effects of Echinacea purpurea extracts (EPE), Ganoderma lucidum extracts (GE) and the mixture (AG) on influenza A/B virus infection. To determine whether EPE and GE enhanced the cell immunity to prevent virus infection or directly suppress virus. The cell survival assay and hemagglutination assay (HA assay) were used in this study. Cells treated with different samples and incubated with influenza A/B showed that all samples enhanced cell survival against virus infevtion. In HA assay, AG and EPE showed good inhibition on influenza A / B viruses. All the samples could improve mitochondrial membrane potential and resist influenza A/B virus infection. EPE and GE at noncytotoxic concentrations increased cell viability but only AG and EPE could directly decrease influenza virus titers. In conclusion, results illustrated the ability of EPE and GE to prevent virus from entering cells by improving cell viability and mitochondrial dysfunction and EPE showed direct inhibition on viruses and prevented viral infection at post-infection strategy.The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerge various of mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting more than 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of COVID-19 virus to cells, which is suitable to see the acute change in cell owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removing pseudovirus, high amounts of ferrous ion were accumulated in mitochondria and then released into cytosol, reactive oxygen species (ROS) accumulation were formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Co Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Co Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ion and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement on mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and released into cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Co Q10 and EPE were effective nutritional strategy to suppress the ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction.紫錐菊靈芝乳鐵蛋白輔酶Q10流感病毒長新冠Echinacea purpureaGanoderma lucidumLactoferrinCo Q10Influenza virusLong-COVID以病毒感染細胞模式探討A/B型流感病毒感染之預防及改善長新冠的營養策略thesis