Journal of ethnopharmacology · 2026
Lusianthridin alleviates inflammatory responses and enhances protective autophagy via downregulation of c-Myc to ameliorate acute lung injury.
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Li Ye, Li Ang, Zhang Weiquan, Zhang Jiaozhen, Li Juan, Wang Yongjie
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Lusianthridin (Lu) is a natural dihydrophenanthrene compound isolated from medicinal orchids including Bletilla striata Rchb.f. and Dendrobium venustum Teijsm. & Binn., which have been traditionally used in East Asian ethnomedicine for the treatment of pulmonary ailments such as cough, hemoptysis, and inflammatory disorders. However, the pharmacological effects and molecular mechanisms of Lu in acute lung injury (ALI) remain unexplored.
AIM OF THE STUDY: This study aimed to investigate whether Lu protects against ALI and to identify its molecular mechanism, with a particular focus on the transcription factor c-Myc as a potential therapeutic hub.
MATERIALS AND METHODS: The anti-inflammatory and autophagy-modulating effects of Lu were evaluated using CuSO4-induced zebrafish, LPS-induced mouse ALI models, and LPS/IFN-γ-stimulated RAW264.7 macrophages. Pulmonary pathology, edema, and inflammatory cytokines were evaluated in LPS-induced mice. NO and ROS levels, protein expression (Western blotting), and autophagic flux were assessed in LPS/IFN-γ-stimulated RAW264.7 cells. Mechanistic studies integrated transcriptomics, molecular docking, molecular dynamics simulations, and genetic knockdown/overexpression approaches (c-Myc siRNA and overexpression plasmids).
RESULTS: Lu significantly reduced inflammatory cell migration, pulmonary pathology, edema, and inflammatory cytokine production. Transcriptomics and molecular docking suggested that Lu interacts with the c-Myc/Max heterodimer, downregulating c-Myc expression. This downregulation subsequently inhibited the pro-inflammatory JAK2-STAT1/3 pathway and reduced iNOS and TNF-α expression. Concurrently, Lu relieved c-Myc-mediated suppression of protective autophagy, as evidenced by enhanced p62 degradation, increased LC3B-II conversion, upregulation of the mitophagy marker PINK1, restoration of mitochondrial membrane potential, and reduced BAX/Bcl-2 ratio. Genetic experiments confirmed that c-Myc knockdown phenocopied Lu effects, while c-Myc overexpression abolished Lu-induced protection.
CONCLUSION: Both in vitro and in vivo models confirmed that Lu significantly attenuates pulmonary inflammation and injury in a c-Myc-dependent manner. These findings not only elucidate the molecular mechanism of Lu but also validate the ethnopharmacological use of medicinal orchids in pulmonary inflammatory conditions, positioning c-Myc as a promising therapeutic target for ALI intervention.
AIM OF THE STUDY: This study aimed to investigate whether Lu protects against ALI and to identify its molecular mechanism, with a particular focus on the transcription factor c-Myc as a potential therapeutic hub.
MATERIALS AND METHODS: The anti-inflammatory and autophagy-modulating effects of Lu were evaluated using CuSO4-induced zebrafish, LPS-induced mouse ALI models, and LPS/IFN-γ-stimulated RAW264.7 macrophages. Pulmonary pathology, edema, and inflammatory cytokines were evaluated in LPS-induced mice. NO and ROS levels, protein expression (Western blotting), and autophagic flux were assessed in LPS/IFN-γ-stimulated RAW264.7 cells. Mechanistic studies integrated transcriptomics, molecular docking, molecular dynamics simulations, and genetic knockdown/overexpression approaches (c-Myc siRNA and overexpression plasmids).
RESULTS: Lu significantly reduced inflammatory cell migration, pulmonary pathology, edema, and inflammatory cytokine production. Transcriptomics and molecular docking suggested that Lu interacts with the c-Myc/Max heterodimer, downregulating c-Myc expression. This downregulation subsequently inhibited the pro-inflammatory JAK2-STAT1/3 pathway and reduced iNOS and TNF-α expression. Concurrently, Lu relieved c-Myc-mediated suppression of protective autophagy, as evidenced by enhanced p62 degradation, increased LC3B-II conversion, upregulation of the mitophagy marker PINK1, restoration of mitochondrial membrane potential, and reduced BAX/Bcl-2 ratio. Genetic experiments confirmed that c-Myc knockdown phenocopied Lu effects, while c-Myc overexpression abolished Lu-induced protection.
CONCLUSION: Both in vitro and in vivo models confirmed that Lu significantly attenuates pulmonary inflammation and injury in a c-Myc-dependent manner. These findings not only elucidate the molecular mechanism of Lu but also validate the ethnopharmacological use of medicinal orchids in pulmonary inflammatory conditions, positioning c-Myc as a promising therapeutic target for ALI intervention.