Jiang Shuai, Xu Xuezeng, Deng Chao, Tian Jiayin, Wang Xue, Liu Lu, Liu Xiaoyi, Zhou Kaixin, He Wei, Yang Yang, Ni Yunfeng
Department of Thoracic Surgery, Tangdu Hospital, The Airforce Medical University, 1 Xinsi Road, Xi'an 710038, China; Department of Chemistry, School of Pharmacy, The Air Force Medical University, 169 Changle West Road, Xi'an 710032, China.
Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, 127 Changle West Road, Xi'an 710032, China.
Phytomedicine. 2025 Aug;144:156443. doi: 10.1016/j.phymed.2025.156443. Epub 2025 Feb 1.
Sepsis, a life-threatening systemic inflammatory syndrome arising from dysregulated host response to pathogenic invasion, often leads to progressive multi-organ dysfunction, wherein acute lung injury typically precedes the onset of extrapulmonary organ failures. Psoralidin (PSO), extracted from Psoralea corylifolia L. seeds, possesses various pharmacological properties, including anti-inflammatory activity, antibacterial efficacy, and antioxidant capacity.
This study aims to elucidate the therapeutic potential and underlying molecular mechanisms of PSO in attenuating sepsis-induced acute lung injury.
Effects of PSO pretreatment on sepsis-induced lung injury were assessed in cecal ligation and puncture (CLP) mice by evaluating sepsis scores, pulmonary cellular apoptosis, histopathological architecture, ROS generation, and TLR2/MyD88/NF-κB signaling. Transcriptomic profiling was performed to elucidate the molecular mechanisms underlying PSO-mediated protection against CLP-induced acute lung injury. To establish an optimal LPS-induced injury model, dose- and time-dependent effects of PSO on cellular morphology and vitality in LPS-challenged MLE-12 pulmonary epithelial cells were assessed. Effects of TLR2 siRNA and TLR2 overexpression on LPS-induced injury in MLE-12 pulmonary epithelial cells were also evaluated..
Pharmacological pretreatment with PSO demonstrated significant efficacy in mitigating sepsis-induced acute lung injury in murine models, as evidenced by improved clinical parameters (reduced sepsis scores and restored anal temperature) and preserved pulmonary histoarchitecture. Transcriptomic profiling revealed that the pulmonary protective effects of PSO are mediated through modulation of the TLR2/MyD88/NF-κB signaling axis. In vitro investigations further demonstrated that PSO pretreatment effectively attenuated LPS-induced oxidative stress through reduction of intracellular ROS accumulation and suppression of TLR2-mediated inflammatory signaling, as indicated by downregulation of key pathway components (NF-κB p65, phosphorylated NF-κB p65, and Caspase1 p20). The critical role of TLR2 in PSO-mediated protection was substantiated through genetic overexpression studies, wherein TLR2 upregulation abrogated the cytoprotective effects of PSO against LPS-induced cellular injury.
PSO exerts significant protection against sepsis-induced acute lung injury by regulating the TLR2/MyD88/NF-κB signaling pathway, effectively attenuating the inflammatory response and oxidative stress. This study provides a theoretical basis for using PSO as a potential lung-protective agent and treatment for sepsis-induced acute lung injury.
脓毒症是一种因宿主对病原体入侵的反应失调而引发的危及生命的全身性炎症综合征，常导致进行性多器官功能障碍，其中急性肺损伤通常先于肺外器官功能衰竭出现。补骨脂素（PSO）从补骨脂种子中提取，具有多种药理特性，包括抗炎活性、抗菌功效和抗氧化能力。
本研究旨在阐明PSO减轻脓毒症诱导的急性肺损伤的治疗潜力及潜在分子机制。
通过评估脓毒症评分、肺细胞凋亡、组织病理学结构、活性氧生成以及TLR2/MyD88/NF-κB信号通路，在盲肠结扎和穿刺（CLP）小鼠中评估PSO预处理对脓毒症诱导的肺损伤的影响。进行转录组分析以阐明PSO介导的对CLP诱导的急性肺损伤保护作用的分子机制。为建立最佳的脂多糖（LPS）诱导损伤模型，评估PSO对LPS刺激的MLE-12肺上皮细胞的细胞形态和活力的剂量和时间依赖性影响。还评估了TLR2小干扰RNA（siRNA）和TLR2过表达对MLE-12肺上皮细胞中LPS诱导损伤的影响。
PSO的药理预处理在减轻小鼠模型中脓毒症诱导的急性肺损伤方面显示出显著疗效，临床参数改善（脓毒症评分降低和肛温恢复）以及肺组织结构得以保留证明了这一点。转录组分析表明，PSO的肺保护作用是通过调节TLR2/MyD88/NF-κB信号轴介导的。体外研究进一步表明，PSO预处理通过减少细胞内活性氧积累和抑制TLR2介导的炎症信号有效减轻LPS诱导的氧化应激，关键通路成分（NF-κB p65、磷酸化的NF-κB p65和半胱天冬酶1 p20）的下调表明了这一点。通过基因过表达研究证实了TLR2在PSO介导的保护中的关键作用，其中TLR2上调消除了PSO对LPS诱导的细胞损伤的细胞保护作用。
PSO通过调节TLR2/MyD88/NF-κB信号通路对脓毒症诱导的急性肺损伤发挥显著保护作用，有效减轻炎症反应和氧化应激。本研究为将PSO用作潜在的肺保护剂及治疗脓毒症诱导的急性肺损伤提供了理论依据。
