Gastrodia elata Blume extract alleviates sepsis-induced lung injury by suppressing IL-23/IL-17 A axis

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.