{"title":"Dendrobine Alleviates LPS-Induced Acute Lung Injury via Activation of the PI3K/AKT/GSK3β Pathway.","authors":"Jia Zhou, Sanzhong Li, Zhenguo Zeng","doi":"10.1016/j.jep.2025.119634","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>To elucidate the anti-inflammatory and antioxidant effects of dendrobine in sepsis-associated ALI and explore its underlying mechanisms in a sepsis mouse model.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119634"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.119634","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: 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.
Aim of the study: To elucidate the anti-inflammatory and antioxidant effects of dendrobine in sepsis-associated ALI and explore its underlying mechanisms in a sepsis mouse model.
Materials and methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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