Ginsenoside Rg3 ameliorates acute exacerbation of COPD by suppressing neutrophil migration

• Published in: International immunopharmacology Vol. 83; p. 106449
• Main Authors: Guan, Xuewa, Yuan, Yuze, Wang, Guoqiang, Zheng, Ruipeng, Zhang, Jing, Dong, Bing, Ran, Nan, Hsu, Alan Chen-Yu, Wang, Cuizhu, Wang, Fang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2020; Elsevier BV
• Subjects: 1-Phosphatidylinositol 3-kinase; Acute exacerbation of chronic obstructive pulmonary disease; Animal models; Animals; Anti-Inflammatory Agents - therapeutic use; Anticancer properties; Cell activation; Cell culture; Cells, Cultured; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette Smoking - adverse effects; Disease Models, Animal; Disease Progression; Epithelial cells; Exposure; Female; Ginseng; Ginsenosides; Ginsenosides - therapeutic use; Ginsenosides Rg3; Global health; Haemophilus Infections - therapy; Haemophilus influenzae - physiology; Humans; Immune System Diseases; Immunology; Infections; Kinases; Leukocyte Disorders; Leukocyte migration; Leukocytes (neutrophilic); Lung - immunology; Lung - pathology; Lung diseases; Lung morphology; Mice; Mice, Inbred BALB C; Neutrophil migration; Neutrophilia; Neutrophils; Obstructive lung disease; Panax - immunology; Pathogenesis; Phosphatidylinositol; Phosphatidylinositol 3-Kinases - metabolism; PI3K; Public health; Pulmonary Disease, Chronic Obstructive - therapy; Respiratory function; Respiratory Mucosa - metabolism; Smoke; Neutrophil migration; PI3K; Acute exacerbation of chronic obstructive pulmonary disease; Ginsenosides Rg3
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106449

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Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is an irreversible inflammatory airways disease responsible for global health burden, involved with a complex condition of immunological change. Exacerbation-mediated neutrophilia is an important factor in the pathogenesis of cigarette smoke-induced AECOPD. Ginsenoside Rg3, a red–ginseng–derived compound, has multiple pharmacological properties such as anti-inflammatory and antitumor activities. Here, we investigated a protective role of Rg3 against AECOPD, focusing on neutrophilia. 14-week-cigarette smoke (CS) exposure and non–typeable Haemophilus inflenzae (NTHi) infection were used to establish the AECOPD murine model. Rg3 (10, 20, 40 mg/kg) was administered intragastrically from the 12th week of CS exposure before infection, and this led to improved lung function and lung morphology, and reduced neutrophilic inflammation, indicating a suppressive effect on neutrophil infiltration by Rg3. Further investigations on the mechanism of Rg3 on neutrophils were carried out using bronchial epithelial cell (BEAS-2B) and neutrophil co-culture and transepithelial migration model. Pre–treatment of neutrophils with Rg3 reduced neutrophil migration, which seemed to be the result of inhibition of phosphatidylinositol (PtdIns) 3–kinases (PI3K) activation within neutrophils. Thus, Rg3 could inhibit exacerbation-induced neutrophilia in COPD by negatively regulating PI3K activities in neutrophils. This study provides a potential natural drug against AECOPD neutrophil inflammation.