Wang Xiaoxue, Ren Weilian, Wang Ping, Dong Li, Du Haitao, Li Na, Liu Guixia, Zhang Ru, Wang Lin, Sun Tiefeng
Department of Clinical Pharmacy, Zhucheng People's Hospital, Weifang, Shandong Province, China.
Department of Anesthesiology, Jinan Children's Hospital, Jinan, Shandong Province, China.
Heliyon. 2024 Sep 21;10(19):e38285. doi: 10.1016/j.heliyon.2024.e38285. eCollection 2024 Oct 15.
Pulmonary infections resulting from respiratory syncytial virus (RSV) continue to pose a significant threat to the well-being of infants and the elderly, but there is no safe, effective and specific treatment except symptomatic treatment. Leaf (FSL) is cold in nature and bitter in taste, and has the efficacy of clearing away heat and toxic materials. Previous research by our research group showed that the active components in FSL have the pharmacological effect of anti-RSV. Based on that, this study aims further to clarify the anti-RSV active components and mechanism of FSL.
Firstly, we established the BALB/c mouse model of RSV infection, assessed the anti-RSV efficacy, and determined the optimal dosage of FSL and its active components. Evaluation parameters included body weight changes, organ indices, lung tissue pathological sections, lung tissue viral load, and inflammatory factors. Additionally, we used RT-PCR, Western Blot and other molecular biology techniques to determine the expression changes of key factors such as Nrf2 and NLRP3 in PI3K/Akt-NLRP3 pathway, and revealed the anti-RSV mechanism of FSL and its active components.
Pharmacodynamic experiments in animals showed that the FSL Low (0.4 g/kg·d), RosA Low (100 mg/kg·d) and Phillyrin Medium (100 mg/kg·d) groups could effectively improve the pathological conditions of mice with RSV pneumonia, such as weight loss, the level of pulmonary inflammatory factors and the increase of viral load. In addition, oral administration of Phillyrin at a dose of 100 mg/kg d to RSV-infected mice can effectively control the trend that the expression of Nrf2 protein decreases and the expression of NLRP3 protein increases in RSV pneumonia mice.
Phillyrin, the active component in FSL, can not only directly inhibit the replication of RSV, but also effectively control the inflammatory reaction caused by RSV infection and improve lung injury, which is expected to become a potential drug against RSV pneumonia.
呼吸道合胞病毒（RSV）引起的肺部感染继续对婴儿和老年人的健康构成重大威胁，但除对症治疗外，尚无安全、有效且特异性的治疗方法。叶下珠（FSL）性寒味苦，具有清热解毒功效。本研究小组先前的研究表明，FSL中的活性成分具有抗RSV的药理作用。基于此，本研究旨在进一步阐明FSL的抗RSV活性成分及作用机制。
首先，建立BALB/c小鼠RSV感染模型，评估抗RSV疗效，确定FSL及其活性成分的最佳剂量。评估参数包括体重变化、脏器指数、肺组织病理切片、肺组织病毒载量及炎症因子。此外，采用RT-PCR、Western Blot等分子生物学技术，检测PI3K/Akt-NLRP3通路中Nrf2和NLRP3等关键因子的表达变化，揭示FSL及其活性成分的抗RSV机制。
动物药效学实验表明，FSL低剂量组（0.4 g/kg·d）、粉防己碱低剂量组（100 mg/kg·d）和连翘苷中剂量组（100 mg/kg·d）可有效改善RSV肺炎小鼠的病理状况，如体重减轻、肺部炎症因子水平及病毒载量增加等。此外，以100 mg/kg d的剂量给RSV感染小鼠口服连翘苷，可有效控制RSV肺炎小鼠中Nrf2蛋白表达降低和NLRP3蛋白表达增加的趋势。
FSL中的活性成分连翘苷不仅能直接抑制RSV复制，还能有效控制RSV感染引起的炎症反应，改善肺损伤，有望成为抗RSV肺炎的潜在药物。
