Gingerol-Rich Extract Derived from Zingiber officinale Roscoe Alleviates Motion Sickness via Inhibiting the Ileal IL-33/ST2/PLC-γ1/TRPA1 Pathway.

Gingerol-rich extract derived from Zingiber officinale Roscoe (ZOGE) is clinically effective against motion sickness (MS), yet its mechanism remains unknown. Here, we demonstrate that ZOGE confers protection by modulating a specific gut-brain immune-neuroendocrine pathway. Using a rotation-induced rat model combined with behavioral tests, vestibular nuclei (VN) metabolomics, and molecular analyses, we found that ZOGE not only alleviated MS symptoms and normalized VN metabolic disturbances, particularly in phenylalanine, tyrosine, and tryptophan biosynthesis, but also potently suppressed the peripheral IL-33/ST2/PLC-γ1/TRPA1 signaling axis in the ileum, leading to reduced synthesis and release of 5-HT, a key MS mediator. Our study provides the evidence that ZOGE acts through coordinated central metabolic modulation and peripheral inhibition of a defined pro-emetic pathway, establishing a novel gut-brain immune-neuroendocrine mechanism for its therapeutic efficacy against MS.