Quercetin 3-O-xyloside ameliorates acute pancreatitis in vitro via the reduction of ER stress and enhancement of apoptosis

Background and purpose: Glycosylation of phenolic compounds has been reported to increase water-solubility, reduce toxicity, and sometimes give improved or novel pharmacological activities. Present study was aimed to evaluate and compare the beneficial effects of quercetin aglycone (Quer) and its glycosylated derivative, quercetin 3-O-xyloside (Quer-Xyl), against acute pancreatitis (AP). Methods: The cellular acute pancreatitis model was established by treating the rat pancreatic acinar cells (AR42J) with lipopolysaccharide (10 µg/ml) and cerulein (10 ⁻⁷ M). The cytotoxicity of Quer or Quer-Xyl on AR42J cells was assessed by MTT assay. Calcium and ROS levels were fluorometrically determined. The ER stress levels (PERK, GRP78), expression levels of amylase and lipase, and apoptotic markers (caspase-3 and -9) were measured by RT-PCR, western blotting, or fluorometric assay. Results: While Quer increased the mRNA expressions of AP marker enzymes, amylase and lipase, Quer-Xyl dose-dependently reversed their expressions. Quer-Xyl suppressed intracellular ROS production and both mRNA and protein levels of GRP78 and PERK, which were significantly elevated in cerulein and LPS-treated AR42J cells. Further, RT-PCR and fluorescence assay revealed that Quer-Xyl dose-dependently augmented the mRNA expressions and activities of caspase-3 and -9. Conclusion: These results showed that Quer-Xyl, but not Quer, has a significant anti-pancreatitis activity through attenuating intracellular ROS production and ER stress response and enhancing apoptotic cell death, suggesting that it might be useful as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat AP.