Zhou Jia, Li Sanzhong, Zeng Zhenguo
Department of Critical Care Medicine, Medical Center of Anesthesiologyand Pain, The First Affliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China; Jiangxi Institute of Respiratory Disease, Nanchang, 330052, China.
Department of Blood Transfusion, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
J Ethnopharmacol. 2025 Apr 25;346:119634. doi: 10.1016/j.jep.2025.119634. Epub 2025 Mar 13.
Dendrobine, a bioactive compound isolated from the traditional Chinese medicinal herb, Dendrobium nobile Lindl, is recognized for its anti-inflammatory and antioxidant properties. However, its role and precise mechanisms in sepsis-associated acute lung injury (ALI) remain unexplored.
To elucidate the anti-inflammatory and antioxidant effects of dendrobine in sepsis-associated ALI and explore its underlying mechanisms in a sepsis mouse model.
A mouse model and THP-1 cells were established to assess protective effects of dendrobine against lipopolysaccharide (LPS)-triggered pathological damage to mouse lung tissue and inflammatory cytokine secretion. Network pharmacology, molecular docking, and Cellular Thermal Shift Assay experiments were employed to identify potential targets and signaling pathways associated with dendrobine. Furthermore, the application of LY294002, a selective inhibitor of PI3K, has allowed for a more precise elucidation of the molecular mechanisms underlying the protective effects of dendrobine.
Dendrobine alleviated LPS-induced lung injury and inflammatory responses in a dose-dependent manner. We identified key targets of dendrobine and related pathways. Specifically, dendrobine activated the PI3K/AKT/GSK3β signaling cascade, which inhibited the production of inflammatory factors such as TNF-α and IL-6, and reduced reactive oxygen species (ROS) levels. This mechanism protected cells from LPS-induced damage. Furthermore, treatment with the PI3K inhibitor LY294002 counteracted the protective effects of dendrobine, thereby confirming the critical role of the PI3K/AKT/GSK3β axis in mediating its anti-inflammatory and cytoprotective functions.
This study, for the first time, demonstrates that dendrobine alleviates LPS-induced tissue damage in sepsis via the PI3K/AKT/GSK3β pathway. These findings highlight the potential of dendrobine as a therapeutic agent against sepsis-induced ALI.
石斛碱是从传统中药铁皮石斛中分离出的一种生物活性化合物，以其抗炎和抗氧化特性而闻名。然而，其在脓毒症相关急性肺损伤（ALI）中的作用及确切机制仍未得到探索。
阐明石斛碱在脓毒症相关ALI中的抗炎和抗氧化作用，并在脓毒症小鼠模型中探索其潜在机制。
建立小鼠模型和THP-1细胞，以评估石斛碱对脂多糖（LPS）引发的小鼠肺组织病理损伤和炎性细胞因子分泌的保护作用。采用网络药理学、分子对接和细胞热位移分析实验来鉴定与石斛碱相关的潜在靶点和信号通路。此外，使用PI3K的选择性抑制剂LY294002，能够更精确地阐明石斛碱保护作用的分子机制。
石斛碱以剂量依赖性方式减轻LPS诱导的肺损伤和炎症反应。我们确定了石斛碱的关键靶点和相关通路。具体而言，石斛碱激活PI3K/AKT/GSK3β信号级联反应，抑制TNF-α和IL-6等炎性因子的产生，并降低活性氧（ROS）水平。这一机制保护细胞免受LPS诱导的损伤。此外，用PI3K抑制剂LY294002处理可抵消石斛碱的保护作用，从而证实PI3K/AKT/GSK3β轴在介导其抗炎和细胞保护功能中的关键作用。
本研究首次证明石斛碱通过PI3K/AKT/GSK3β途径减轻脓毒症中LPS诱导的组织损伤。这些发现凸显了石斛碱作为治疗脓毒症诱导的ALI药物的潜力。
