Notoginsenoside R1 restrains the proliferation and migration of airway smooth muscle cells isolated from rats with chronic obstructive pulmonary disease

Abstract

Objective Chronic obstructive pulmonary disease (COPD) is a common disorder that is characterized by systemic and lung inflammation. Notoginsenoside R1 (NGR1) displays anti-inflammatory properties in numerous diseases. We aimed to explore the function and mechanism of NGR1 in COPD. Materials and methods COPD rats were established through cigarette smoke exposure, lipopolysaccharide injection, and cold stimulation. Rat airway smooth muscle cells (ASMCs) were separated and identified. Then, ASMCs were treated with NGR1 (25 or 50 μM) and cigarette smoke extract (CSE). Thereafter, the vitality, proliferation, and migration of ASMCs were measured. Additionally, cell cycle, inflammation-related factors, α-SMA, and PI3K/AKT pathway-related marker expressions of the ASMCs were also detected. Molecular docking experiments were conducted to explore the interaction of NGR1 to PI3K, TGF-β, p65, and AKT. Moreover, 740 Y-P (a PI3K/Akt pathway agonist) were used to validate the mechanism of NGR1 on COPD. Results NGR1 inhibited the proliferation and migration, but caused cell cycle arrest for CSE-triggered ASMCs. Furthermore, NGR1 not only decreased IL-1β, IL-6, IL-8, and TNF-α contents, but also reduced α-SMA expression in CSE-stimulated ASMCs. Moreover, NGR1restrainedTGF-β1 expression, PI3K, p65, and AKT phosphorylation in CSE-stimulated ASMCs. Molecular docking experiments showed NGR1 exhibited a strong binding ability to PI3K, TGF-β1, p65, and AKT. Notably, the effects of NGR1 on the proliferation and migration of CSE-induced ASMCs were reversed by 740 Y-P. Conclusions NGR1 can restrain the proliferation and migration of CSE-induced ASMCs, indicating that NGR1 may be a therapeutic candidate for treating COPD.