Polydatin inhibits mitochondrial damage and mitochondrial ROS by promoting PINK1-Parkin-mediated mitophagy in allergic rhinitis.

Abstract

Polydatin (PD), a natural product derived from Polygonum cuspidatum, has anti-inflammatory and antioxidant effects and has significant benefits in treating allergic diseases. However, its role and mechanism in allergic rhinitis (AR) have not been fully elucidated. Herein, we investigated the effect and mechanism of PD in AR. AR model was established in mice with OVA. Human nasal epithelial cells (HNEpCs) were stimulated with IL-13. HNEpCs were also treated with an inhibitor of mitochondrial division or transfected with siRNA. The levels of IgE and cellular inflammatory factors were examined by enzyme linked immunosorbent assay and flow cytometry. The expressions of PINK1, Parkin, P62, LC3B, NLRP3 inflammasome proteins, and apoptosis proteins in nasal tissues and HNEpCs were measured by Western blot. We found that PD suppressed OVA-induced epithelial thickening and eosinophil accumulation in the nasal mucosa, reduced IL-4 production in NALF, and regulated Th1/Th2 balance. In addition, mitophagy was induced in AR mice after OVA challenge and in HNEpCs after IL-13 stimulation. Meanwhile, PD enhanced PINK1-Parkin-mediated mitophagy but decreased mitochondrial reactive oxygen species (mtROS) production, NLRP3 inflammasome activation, and apoptosis. However, PD-induced mitophagy was abrogated after PINK1 knockdown or Mdivi-1 treatment, indicating a key role of the PINK1-Parkin in PD-induced mitophagy. Moreover, mitochondrial damage, mtROS production, NLRP3 inflammasome activation, and HNEpCs apoptosis under IL-13 exposure were more severe after PINK1 knockdown or Mdivi-1 treatment. Conclusively, PD may exert protective effects on AR by promoting PINK1-Parkin-mediated mitophagy, which further suppresses apoptosis and tissue damage in AR through decreasing mtROS production and NLRP3 inflammasome activation.