Yu Ping Feng San Protects Mice Against Porcine Pancreatic Elastase-Induced Emphysema by Blunting Innate Immune Response

Abstract

Yu Ping Feng San (YPFS) is an effective TCM formula for the treatment of asthma, allergic rhinitis, and primary nephrotic syndrome; it was also found to significantly reduce exacerbation rate and the risk of a second exacerbation in COPD patients. However, the efficacy of YPFS in treating emphysema is not entirely understood. This study aims to investigate the protective effects of YPFS on the compromised lung function and increased systemic and lung inflammation during the emphysema development. We developed an emphysema mice model using porcine pancreatic elastase (PPE) and treated it with YPFS (1950, 975, and 487.5 mg/kg/d) or Dexamethasone (Dex, 2 mg/kg/d) once daily for 32 days, beginning on day 4 before PPE exposure. On day 7 post-PPE challenge, peripheral leucocytes and inflammatory cells in lungs were analyzed by blood cell analyzer and flow cytometry, respectively. Pulmonary inflammatory mediators were determined by Bio-Plex or ELISA assay. The invasive lung function was measured on day 28. In addition, histopathological changes at both time points were assessed, and the mean linear intercept (MLI) was calculated. The results showed that YPFS significantly improved the decline in FEV100 and Cdyn as well as the increase in RI. YPFS also reduced the severity of emphysema development, as reflected by a decrease in MLI. For anti-inflammatory evaluation, YPFS reduced levels of IL-1β, IL-6, IL-8, KC, MCP-1, and MMP-9 in the lungs and significantly inhibited the accumulation of resident alveolar macrophages but had no effect on the levels of T cells, CD4+ T cells, and CD8+ T cells. In conclusion, YPFS blunted the innate immune response in mice exposed to PPE, thereby preventing the development of emphysema. This finding indicates the potential of YPFS as an adjunct treatment for individuals with COPD emphysematous phenotype.

Note:
Funding declaration: This study was funded by National Administration of Traditional Chinese Medicine (ZYYCXTU-D-202203), the National Natural Science Foundation of China (81872765), Guangdong Academy of Sciences (2020GDASYL-20200103046), Young top talent of science and Technology Innovation Department of Guangdong Province (2021TQ060189), Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease (GHMJLRID-Z-202105)，Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020012，ZNSA-2020013)，Open Project of State Key Laboratory of Respiratory Disease (SKLRD-OP-202215)，and Guangdong Basic and Applied Basic Research Foundation (2020B1515120045, 2020A1515110151).

Conflict of Interests: The authors declare no conflict of interest.

Ethical Approval: Animal experiments were conducted under a protocol approved by the ethics committee of Laboratory Animal Center (Authorized number: W220007), Zhongshan Development Zone Laboratory Animal Center, Guangzhou Analysis and Testing Center, China

Keywords: Yu Ping Feng San, Emphysema, Inflammation, Innate immunity