Dihydromyricetin Blocks SYVN1-Mediated Degradation of SLC7A11 to Suppress Ferroptosis and Promote Gastric Repair.

Gastric ulcer is a prevalent clinical condition. Although current clinical management with proton pump inhibitors and Helicobacter pylori eradication is highly effective, there remains a need for early intervention strategies that directly promote gastric mucosal repair and prevent ulcer recurrence. This study demonstrates that dihydromyricetin (DHM), a natural flavonoid compound found in abundance in vine tea, alleviates gastric mucosal injury and promotes repair in rats via inhibiting ferroptosis. Mechanistically, DHM was proved to suppress oxidative stress and ferroptosis by activating the SLC7A11/GPX4 signaling pathway. Furthermore, DHM directly stabilizes SLC7A11 and promotes its membrane localization by disrupting binding with its E3 ubiquitin ligase SYVN1, thereby inhibiting SYVN1-mediated K48-linked ubiquitination at K30, K37, and K483. Moreover, DHM exerts protective effects in human-derived gastric organoid models, promoting growth and morphological repair. Collectively, DHM promotes gastric repair by suppressing ferroptosis via blocking SYVN1-dependent SLC7A11degradation.