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 antiinflammatory 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 OVAinduced 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

Doxorubicin-Induced Cardiac Senescence Is Alleviated Following Treatment with Combined Polyphenols and Micronutrients through Enhancement in Mitophagy

“…In particular, BNIP3dependent mitophagy seems to play an important role in limiting mitochondrial ROS levels [43], and, in our system, the involvement of BNIP3 in the protective effects of A5 + was evident in H9C2-treated cells but even more so after A5 + pre-treatment in DOXOinduced senescent H9C2 cells. Interestingly, it has been recently demonstrated that, in allergic rhinitis, Polydatin inhibits mitochondrial damage and mitochondrial ROS by promoting PINK1-Parkin-mediated mitophagy similarly to what we showed for A5 + [44].…”

Screening anti‐anaphylactoid components in Polygonum cuspidatum via cell membrane chromatography with LC‐MS targeting Mas‐related G protein‐coupled receptor X2

“…PC, a traditional Chinese medicine, is recognized for its anti-inflammatory and antioxidant properties, demonstrating significant efficacy in treating allergic diseases [6,7]. Therefore, we selected PC for practical application in the aforementioned screening system, and the screening results are depicted in Figure 3.…”

“…Despite the critical role of MrgprX2 in anaphylaxis, there is a lack of therapeutic agents directly targeting it. Polygonum cuspidatum (PC), a traditional Chinese medicine, has been reported for its anti-allergic activities [6][7][8]. While the specific components responsible remain undefined.…”

Traditional herbs: mechanisms to combat cellular senescence

“…In studies based on hydrogen peroxide-induced senescence in HUVEC and human nucleus pulposus cells (NPC), resveratrol was found to attenuate mitochondrial dysfunction through autophagy, thereby delaying cellular senescence [106,107]. In human nasal epithelial cell stress-based and mouse allergic rhinitis models, Polydatin ameliorated mitochondrial damage through PINK1-Parkin-mediated mitochondrial autophagy and exerted a protective effect against allergic rhinitis by inhibiting NLRP3 inflammatory vesicles [108].…”