Erianin ameliorates morphine tolerance and glioma progression through the JAK2-STAT3 pathway

Abstract

Prolonged morphine use and glioma-induced stress have a significant impact on pain management outcomes and tumor progression. This study investigates Erianin’s potential to alleviate morphine tolerance and inhibit glioma progression through its modulation of the JAK2/STAT3 pathway. Glioma-bearing morphine-tolerant mouse models were used to evaluate Erianin’s effects on analgesia, tumor growth, and molecular pathways. Erianin administration effectively reduced morphine tolerance (50 % inhibition rate) and glioma progression (60 % inhibition rate) by inhibiting the JAK2/STAT3 signaling and suppressing BDNF expression in dorsal root ganglia (DRG). Multi-omics analysis (integrating transcriptomics and miRNA-seq data) highlighted key roles of miR-375 and miR-20a in targeting JAK2, demonstrating their critical involvement in regulating morphine tolerance and glioma-induced neuroinflammation. Further, chronic morphine use was identified as modulators of the JAK2-STAT3 pathway dysregulation. These findings uncover the potential of Erianin as a therapeutic agent. Specifically, we reveal druggable targets within inflammatory signaling cascades, providing molecular blueprints for precision interventions in pain-related oncology care.