Walnut polyphenol extracts inhibit <i>Helicobacter pylori</i>-induced STAT3<sup>Tyr705</sup> phosphorylation through activation of PPAR-γ and SOCS1 induction

Abstract

The health beneficial effects of walnut plentiful of <i>n</i>-3 polyunsaturated fatty acid had been attributed to its anti-inflammatory and anti-oxidative properties against various clinical diseases. Since we have published <i>Fat</i>-1 transgenic mice overexpressing <i>3-desaturase</i> significantly mitigated <i>Helicobacter pylori</i> (<i>H. pylori</i>)-associated gastric pathologies including rejuvenation of chronic atrophic gastritis and prevention of gastric cancer, in this study, we have explored the underlying molecular mechanisms of walnut against <i>H. pylori</i> infection. Fresh walnut polyphenol extracts (WPE) were found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by <i>H. pylori</i> infection in RGM-1 gastric mucosal cells. Notably, <i>H. pylori</i> infection significantly decreased suppressor of cytokine signaling 1 (SOCS1), but WPE induced expression of SOCS1, by which the suppressive effect of walnut extracts on STAT3^Tyr705 phosphorylation was not seen in SOCS1 KO cells. WPE induced significantly increased nuclear translocation nuclear translocation of PPAR-γ in RGM1 cells, by which PPAR-γ KO inhibited transcription of SOCS1 and suppressive effect of WPE on p-STAT3^Tyr705 was not seen. WPE inhibited the expression of c-<i>Myc</i> and IL-6/IL-6R signaling, which was attenuated in the RGM1 cells harboring SOCS1 specific siRNA. Conclusively, WPE inhibits <i>H. pylori</i>-induced STAT3 phosphorylation in a PPAR-γ and SOCS1-dependent manner.