A New Perspective for Improving COPD: Ginsenoside Rg3 Links SIRT1 to Inhibit Mitochondrial Autophagy.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent yet manageable respiratory condition. However, treatments presently used normally have side effects and cannot cure COPD, making it urgent to explore effective medications. The ginsenoside Rg3 (Rg3) has been shown to have anti-inflammatory and anti-tumor properties and can improve COPD. The primary objectives of this investigation were to explore the impact of Rg3 on COPD and delve into the associated mechanisms.

Methods: models exposed human bronchial epithelial cells (BEAS-2B) to cigarette smoke extract (CSE), and models induced COPD in mice through chronic inhalation of cigarette smoke (CS). Sirtuin 1 (SIRT1) expression was regulated via cell transfection or mice infection with recombinant lentiviruses. mRNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and SIRT protein levels were assessed by western blot or enzyme-linked immunosorbent assays (ELISA). Mitophagy was evaluated by light chain 3 (LC3) II/I and phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) levels, and apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Lung function was measured with the Buxco system, and inflammation was assessed via interleukin 6 (IL-6) and keratinocyte-derived cytokine (KC) levels in bronchial alveolar lavage fluid. Lung morphological impairments were determined through Hematoxylin and Eosin (H&E) staining and mean linear intercept (MLI) measurement.

Results: In BEAS-2B cells, CSE treatment caused a decrease in SIRT1 expression ( < 0.01) and an increase in LC3 II/I ( < 0.01) and PINK1 ( < 0.01), which were all reversed by Rg3 ( < 0.01), with 20 μM Rg3 performing the best and being used subsequently. CSE increased apoptosis of BEAS-2B cells ( < 0.01), which was reversed by Rg3 ( < 0.01). Upregulated SIRT1 further decreased levels of LC3 II/I ( < 0.001), PINK1 ( < 0.001), and cell apoptosis ( < 0.001) for CSE- and Rg3-treated cells, whereas downregulated SIRT1 reversely increased levels of LC3 II/I ( < 0.001), PINK1 ( < 0.001), and cell apoptosis ( < 0.001). The establishment of COPD caused a decrease in SIRT1 mRNA ( < 0.001), SIRT1 protein ( < 0.001), and lung functions ( < 0.001) whereas IL-6 ( < 0.001), KC ( < 0.001), lung impairment, and MLI ( < 0.001) were increased; all of these effects were reversed by Rg3 ( < 0.001). Moreover, the Rg3-induced reversion was furthered by SIRT1 upregulation ( < 0.001) and was disrupted by SIRT1 downregulation ( < 0.001).

Conclusion: Rg3, through activation of SIRT1, suppresses mitophagy and apoptosis, ameliorates COPD, and improves lung functions.