Compound glycyrrhiza oral solution alleviates oxidative stress and inflammation by regulating SRC/MAPK pathway in chronic obstructive pulmonary disease

Immunopharmacol Immunotoxicol. 2022 Dec;44(6):1032-1043. doi: 10.1080/08923973.2022.2102992. Epub 2022 Aug 11.

Abstract

Objectives: Patients with chronic obstructive pulmonary disease (COPD) suffer from persistent cough and breathlessness, which can be ameliorated by the Chinese herbal medicine glycyrrhiza. Furthermore, the SRC/MAPK pathway is activated in the process of oxidative stress and inflammation, which afflict COPD progression. Thus, this research aimed at dissecting the mechanism of compound glycyrrhiza oral solution (CGOS) relieving oxidative stress and inflammation in COPD via the SRC/MAPK pathway.

Methods: After a COPD rat model was established using lipopolysaccharide and cigarette smoke, rats underwent intragastric administration with CGOS and intratracheal injection with LV-NC and LV-SRC lentivirus into lungs. Then, pulmonary function-related indexes were evaluated, followed by analyses of arterial blood and inflammatory cell number in prepared bronchoalveolar lavage fluids. Meanwhile, the contents of oxidative stress-related indicators (malondialdehyde, 3NT, 8-Isoprostane, glutathione, NO, and SOD) in pulmonary tissues were measured, along with RT-qPCR and ELISA detection of the expression of inflammatory factors (TNF-α, IL-1β, IL-4, and IL-10). Moreover, western blot assay was utilized to assess p-SRC/SRC and p-p38/p38 ratios in pulmonary tissues.

Results: CGOS treatment enhanced PaO2 and reduced PaCO2 in COPD rats, accompanied by declines in the number of total cells, neutrophils, and macrophages. CGOS improved pulmonary function, decreased malondialdehyde, 3NT, 8-Isoprostane, TNF-α, and IL-1β levels, and increased GSH, NO, IL-4, and IL-10 levels and SOD activity. Mechanistically, CGOS suppressed the SRC/MAPK pathway, and SRC overexpression reversed the alleviating function of CGOS in COPD rats.

Conclusions: In conclusion, CGOS might alleviate oxidative stress and inflammation in COPD rats by inhibiting the SRC/MAPK pathway.

Keywords: Compound glycyrrhiza oral solution; SRC/MAPK pathway; chronic obstructive pulmonary disease; inflammation; oxidative stress.

MeSH terms

  • Animals
  • Interleukin-10*
  • Interleukin-4
  • Oxidative Stress
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Rats
  • Tumor Necrosis Factor-alpha

Substances

  • Interleukin-10
  • Tumor Necrosis Factor-alpha
  • Interleukin-4