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Rutaecarpine alleviates aspirin-induced gastric injury via oxidative stress and ferroptosis inhibition
Lei Chang1, Shizhang Wei2, Xin Wang3
1Department of Pharmacy, Peking University Cancer Hospital and Institute, Beijing, 100142, China; Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
Introduction:
Rutaecarpine (RUT) has shown potential therapeutic benefits for gastrointestinal disorders, but its molecular mechanisms remain unclear. This study aimed to investigate the molecular mechanism of RUT in treating aspirin-induced acute gastric mucosal injury in rats.
Methods:
SD rats received RUT for 7 consecutive days before aspirin-induced gastric damage. Metabolomics approaches were employed to identify differential metabolic signals and RUT-mediated protective mechanisms, validated by Western blotting.
Results:
Compared to the model group, both RUT doses significantly alleviated gastric mucosal damage by enhancing tight junction-associated protein expression, suppressing inflammatory factors. Metabolomics revealed that the gastroprotective effects of RUT were primarily associated with lipid peroxidation and oxidative stress regulation. Furthermore, RUT treatment markedly reduced 4-HNE and MDA levels, and elevated GSH, SOD, and CAT activities, upregulated protein expression levels of Nrf2, HO-1, SLC7A11, GPX4, and FTH1.
Conclusion:
These findings demonstrate that RUT protects against aspirin-induced gastric mucosal injury by suppressing oxidative stress and inhibiting ferroptosis signaling pathways.
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