Ginsenoside Rb1 Alleviates Asthma Inflammation by Regulating Mitochondrial Dysfunction through SIRT1/PGC-1<i>α</i> and PI3K/AKT Pathways

The aim of this study was to investigate whether ginsenoside Rb1 attenuates cockroach extract (CRE)-induced asthma by interfering with mitochondrial dysfunction. After induction with CRE, mice were administered different doses of Rb1. Hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and flow cytometry analysis revealed that inflammatory cell infiltration, total immunoglobulin E (IgE) and CRE-specific IgE in serum, and inflammatory cytokines in bronchoalveolar lavage fluid were effectively inhibited by Rb1. Through Western blot, TUNEL, and immunofluorescence colocalization assays, we observed Rb1 also inhibited endogenous reactive oxygen species (ROS), tightly associated with increased superoxide dismutase, catalase levels, and decreased malondialdehyde levels. Subsequently, the silent information regulator sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) pathway was activated, whereas the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was inhibited. Additionally, Rb1 could rescue mitochondrial dysfunction by promoting the mitochondrial fusion protein mitofusion 1 (MFN1) and inhibiting dynamin-related protein 1 (DRP1) expression and apoptosis in the lungs. In BEAS-2B cells, Rb1 plays a role similar to that of a SIRT1 agonist (SRT1720), including enhancing mitochondrial membrane potential and decreasing mitochondrial ROS and DRP1 translocation to mitochondria. Our findings suggest that Rb1 maintains mitochondrial integrity by activating SIRT1/PGC-1α and inhibiting PI3K/AKT, thereby ameliorating asthmatic airway inflammation.