Yang Yu, Xu Zhi, Li Qi, Wang Guansong, Xu Jiancheng
Department of Respiratory, The Second Affiliated Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, 400037, China.
Sci Rep. 2025 Sep 26;15(1):33159. doi: 10.1038/s41598-025-91062-4.
Acute lung injury (ALI) is a severe respiratory disease characterized by various clinical manifestations, including intractable hypoxemia, alveolar hypertension, parenchymal edema, and progressive respiratory distress. If left untreated, ALI can progress into acute respiratory distress syndrome (ARDS). A promising therapeutic option for ALI is Pedunculoside (PE), a major bioactive flavonoid found in Butcher's broom (Ruscus aculeatus). PE has been shown to possess significant anti-inflammatory and antioxidant effects. This study aimed to investigate the therapeutic effects of PE on ALI in mice and to understand the underlying mechanism of action. Initially, we established a mouse model of acute lung epithelial cell (MLE-12) injury induced by lipopolysaccharide (LPS). Subsequently, we treated the MLE-12 cells with PE and observed a significant improvement in cell viability and a reduction in apoptosis. Moreover, when ALI mice were treated with PE, we observed an enhancement in lung histopathological structure, a decrease in lung tissue wet-to-dry (W/D) ratio, and reduced total protein concentrations in bronchoalveolar lavage fluid (BALF). Additionally, there was a decrease in apoptotic epithelial cells in lung tissue and an increase in proliferating cells after PE intervention. PE treatment also led to reduced levels of intracellular interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), while increasing glutathione (GSH) levels and superoxide dismutase (SOD) activity in both MLE-12 cell supernatants and BALF of ALI mice. Our mechanistic studies demonstrated that PE effectively downregulated the expression of p-p65 and p-IκBα proteins. However, the induced activation of the transcription factor p65 reversed the regulatory effects of PE, partially counteracting its anti-apoptotic, anti-inflammatory, and antioxidant activities in MLE-12 cells. These findings demonstrate that PE treatment has the potential to mitigate LPS-induced ALI by inhibiting NF-κB signaling-mediated oxidative stress and inflammatory responses.
急性肺损伤（ALI）是一种严重的呼吸系统疾病，其特征为多种临床表现，包括难治性低氧血症、肺泡高压、实质水肿和进行性呼吸窘迫。若不治疗，ALI可进展为急性呼吸窘迫综合征（ARDS）。对ALI而言，一种有前景的治疗选择是扁蓄苷（PE），它是假叶树（刺叶假叶树）中发现的一种主要生物活性黄酮类化合物。已表明PE具有显著的抗炎和抗氧化作用。本研究旨在探究PE对小鼠ALI的治疗效果，并了解其潜在作用机制。最初，我们建立了脂多糖（LPS）诱导的急性肺上皮细胞（MLE-12）损伤小鼠模型。随后，我们用PE处理MLE-12细胞，观察到细胞活力显著改善且凋亡减少。此外，当用PE治疗ALI小鼠时，我们观察到肺组织病理结构得到改善、肺组织湿重与干重（W/D）比值降低以及支气管肺泡灌洗液（BALF）中总蛋白浓度降低。另外，PE干预后肺组织中凋亡上皮细胞减少，增殖细胞增加。PE治疗还导致细胞内白细胞介素（IL）-6、IL-1β、肿瘤坏死因子（TNF）-α和丙二醛（MDA）水平降低，同时增加了MLE-12细胞上清液和ALI小鼠BALF中的谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性。我们的机制研究表明，PE有效下调了p-p65和p-IκBα蛋白的表达。然而，转录因子p65的诱导激活逆转了PE的调节作用，部分抵消了其在MLE-12细胞中的抗凋亡、抗炎和抗氧化活性。这些发现表明，PE治疗有可能通过抑制NF-κB信号介导的氧化应激和炎症反应来减轻LPS诱导的ALI。
