Ginsenoside Rh1 Alleviates Allergic Rhinitis by Mediating Mitochondrial Autophagy via Activation of the...

Ginsenoside Rh1, a bioactive compound derived from ginseng, exhibits notable anti-inflammatory and antioxidant effects and has shown promising therapeutic potential in the treatment of allergic diseases. However, its exact role in allergic rhinitis (AR) and the underlying molecular mechanisms remain inadequately understood. This study investigates whether Rh1 alleviates AR through AMPK/ULK1/FUNDC1-mediated mitochondrial autophagy. In this study, human nasal epithelial cells (HNEpCs) were stimulated with house dust mite (HDM) and treated with mitochondrial autophagy inhibitors or siRNA transfection techniques to assess the effects of Rh1. Network pharmacology and molecular docking (MD) were used to explore the interactions between Rh1 and AMPK, ULK1, and FUNDC1. To explore the effects of Rh1, enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FC) were employed to measure IgE levels and various inflammatory mediators. Western blot (WB) analysis was conducted to assess protein expression related to mitochondrial autophagy, inflammation, and apoptosis in nasal tissues and HNEpCs. Immunofluorescence (IF) and transmission electron microscopy (TEM) provided further verification. The experimental data reveal that Rh1 effectively alleviates HDM-induced nasal mucosal epithelial thickening and eosinophil infiltration by modulating mitochondrial autophagy via the AMPK/ULK1/FUNDC1 signaling pathway. Additionally, Rh1 inhibits IL-4 secretion in nasal airway lavage fluid (NALF) and helps restore the Th1/Th2 immune balance. It also reduces mtROS production, inhibits NLRP3 inflammasome activation, and prevents apoptosis, thereby mitigating tissue damage associated with AR. Knockdown of AMPK or treatment with 3-Methyladenine (3-MA) further confirmed Rh1's inducing effect on mitophagy. In summary, Rh1 modulates mitophagy through the AMPK/ULK1/FUNDC1 pathway, reducing inflammatory responses and inhibiting apoptosis, thereby offering significant protection against AR.