Ginsenoside Rb1 alleviates airway inflammation in asthma by regulating mitochondrial dysfunction through SIRT1/PGC-1α and PI3K/AKT signaling pathway

Aim of this study is to investigate whether Ginsenoside Rb1 attenuates cockroach extract (CRE) induced asthma by interfering with mitochondrial dysfunction. After induction of CRE, mice were administrated different dose of Rb1. HE staining, ELISA and flow cytometry analysis showed that, the inflammatory cell infiltration, total IgE and CRE specific IgE in serum, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were effectively inhibited by Rb1. Through Western blot, TUNEL and immunofluorescence co-localization assay, we observed Rb1 also inhibited endogenous reactive oxygen species (ROS), tightly associated with increased superoxide dismutase (SOD), catalase (CAT) levels, and decreased malondialdehyde (MDA). Subsequently, the silent information regulator Sirtuni1(SIRT1)/peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) pathway were activated, whereas, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were alleviated. All of which led to mitochondria dysfunction via promoting mitochondrial fusion protein Mitofusion 1 (MFN1) and inhibiting dynamin-related protein 1 (DRP1) expression and apoptosis in lungs. In BEAS-2B cells, Rb1 played a similar role as SIRT1 agonist (SRT1720), including mitochondrial membrane potential enhancement, mitochondrial ROS and DRP1 translocation to mitochondria decrease. Our findings suggest that Rb1 maintains mitochondria integrity by activating SIRT1/PGC-1α, inhibiting PI3K/AKT, thereby ameliorates asthmatic airway inflammation.