Dong Huiqing, Zhang Yun, Zhou Yang, Zhang Menghui, Zhang Lei, Feng Jing, Wu Wanying, Liu Yifei, Wang Ting
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China.
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Fitoterapia. 2025 Jul;184:106624. doi: 10.1016/j.fitote.2025.106624. Epub 2025 May 19.
The Compendium of Materia Medica recorded that the traditional Chinese medicine Gastrodia elata Blume (G. elata) has applications in antibacterial and antiviral. GE05 was prepared from the rhizome of G. elata and its active ingredients have been proven to alleviate inflammatory response. However, the protective effect and the underlying mechanism of G. elata in sepsis remain unclear. Our study aims to uncover the efficacy and molecular mechanisms of GE05 in ameliorating sepsis-induced lung injury. Here, we have shown that GE05 could inhibit the expression of inflammatory cytokines in peritoneal macrophages. Bioinformatics analysis showed the activation of interleukin (IL)-17 signaling pathway in acute lung injury (ALI) mice. We established septicemia models and showed that GE05 improves survival rates and protects against sepsis-induced lung injury by downregulating the IL-23/IL-17 A axis. Quantitative real- time PCR (qPCR) analysis and immunohistochemistry have indicated that IL-17 A inhibition reduces the release of chemokine ligand (Cxcl) 1, Cxcl2, granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), mitigating neutrophil infiltration-induced lung tissue damage. Meanwhile, GE05 could inhibit the activation of the IL-17 A-related phosphatidylinositol 3-kinase/ c-Jun N-terminal kinase (PI3K/JNK) signaling pathway, suppressing the expression of tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6. These results demonstrated that GE05 is a promising agent that targets the IL-23/IL-17 A axis, providing new way for preventing and treating sepsis-induced lung injury.
《本草纲目》记载，中药天麻具有抗菌和抗病毒作用。GE05由天麻的根茎制备而成，其活性成分已被证明可减轻炎症反应。然而，天麻在脓毒症中的保护作用及其潜在机制仍不清楚。我们的研究旨在揭示GE05改善脓毒症诱导的肺损伤的疗效和分子机制。在此，我们发现GE05可抑制腹膜巨噬细胞中炎性细胞因子的表达。生物信息学分析显示急性肺损伤（ALI）小鼠中白细胞介素（IL）-17信号通路被激活。我们建立了败血症模型，并表明GE05通过下调IL-23/IL-17 A轴提高生存率并预防脓毒症诱导的肺损伤。定量实时PCR（qPCR）分析和免疫组织化学表明，抑制IL-17 A可减少趋化因子配体（Cxcl）1、Cxcl2、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）的释放，减轻中性粒细胞浸润引起的肺组织损伤。同时，GE05可抑制IL-17 A相关的磷脂酰肌醇3激酶/c-Jun氨基末端激酶（PI3K/JNK）信号通路的激活，抑制肿瘤坏死因子-α（TNF-α）、IL-1β和IL-6的表达。这些结果表明，GE05是一种有前景的靶向IL-23/IL-17 A轴的药物，为预防和治疗脓毒症诱导的肺损伤提供了新途径。
