Bu-Shen-Fang-Chuan formula attenuates cigarette smoke-induced inflammation by modulating the PI3K/Akt-Nrf2 and NF-κB signalling pathways

J Ethnopharmacol. 2020 Oct 28:261:113095. doi: 10.1016/j.jep.2020.113095. Epub 2020 Jun 10.

Abstract

Ethnopharmacological relevance: Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Unlike asthma, COPD is insensitive to glucocorticoid treatment; thus, it is of great importance to find alternative medications, including Chinese medicine, to suppress inflammation. Bu-Shen-Fang-Chuan formula (BSFCF) is commonly used for the treatment of COPD in China. However, the mechanisms of BSFCF in COPD treatment are still unclear.

Aim of the study: To verify the anti-inflammatory efficacy of BSFCF in COPD and to explore the possible mechanisms underlying its anti-inflammatory efficacy based on the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-Nuclear factor erythroid 2-related factor 2 (Nrf2) and Nuclear factor (NF)-κB signalling pathways.

Materials and methods: A rat model of COPD was established by chronic exposure to cigarette smoke (CS) for 6 months. Bronchoalveolar lavage fluid (BALF) and blood were obtained to detect inflammatory cytokines. Lung samples were harvested, and part of each sample was fixed for subsequent H&E staining and immunohistochemical (IHC) analysis. The remaining lung tissues were used for RNA sequencing analysis and western blotting.

Results: BSFCF significantly reduced inflammatory infiltration in the lungs of CS-exposed rats and decreased the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in both the BALF and serum. Additionally, BSFCF evidently attenuated NF-κB activation and downregulation of glucocorticoid receptor (GR) caused by CS. Furthermore, BSFCF increased the activation of PI3K/Akt-Nrf2 signalling in response to CS.

Conclusions: BSFCF attenuated CS-induced inflammation in COPD, which was partially achieved through the PI3K/Akt-Nrf2 and NF-κB signalling pathways.

Keywords: Bu-Shen-Fang-Chuan formula (BSFCF); COPD; Inflammation; Nrf2; PI3K/Akt.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cigarette Smoking*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Lung / drug effects*
  • Lung / enzymology
  • Lung / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Phosphatidylinositol 3-Kinase
  • Phosphorylation
  • Pneumonia / enzymology
  • Pneumonia / etiology
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Bu-Shen-Fang-Chuan
  • Cytokines
  • Drugs, Chinese Herbal
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Receptors, Glucocorticoid
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt