Pingchuan formula attenuates airway mucus hypersecretion via regulation of the PNEC-GABA-IL13-Muc5ac axis in asthmatic mice

Biomed Pharmacother. 2021 Aug:140:111746. doi: 10.1016/j.biopha.2021.111746. Epub 2021 May 29.

Abstract

Background/aims: Asthma is a common chronic respiratory disease. It has been reported that Pingchuan formula (PCF) can control asthma attacks by reducing airway inflammation, muscle spasm and mucus secretion. However, PCF's mechanism for reducing airway mucus hypersecretion remains unclear. This study aimed to investigate the effect of PCF on airway mucus secretion in asthmatic mice and to explore changes in the PNEC-GABA-IL13-Muc5ac axis.

Methods: Male Babl/c mice were used to establish the asthma model via sensitisation with OVA. Mice were randomly divided into Normal, OVA, DEX, and PCF groups. After treatment, lung histopathology was observed with H&E and PAS staining. BALF levels of IL-5 and IL-13 were detected using ELISA. The levels of mRNA and protein expression for GAD1, GABAARβ1, GABAARα1 and Muc5ac in the lung tissue were measured by RT-PCR and Western blot assays. PNECs were observed with AgNOR staining.

Results: PCF treatment effectively reduced goblet cell (P < 0.01) and PNEC (P < 0.05) proliferation, lung tissue inflammation and airway mucus hypersecretion. In addition, PCF also markedly downregulated mRNA and protein expression of GAD1, GABAARβ1, GABAARα1 and Muc5ac (P < 0.05, compared with OVA), thus inhibiting the GABA-IL-13 pathway in the lung tissue of asthmatic mice.

Conclusion: These findings suggest that PCF controls asthma attacks by reducing airway inflammation and mucus hypersecretion via the PNEC-GABA-IL13-Muc5ac axis.

Keywords: Asthma; GABA; PNEC; Pingchuan formula; TCM.

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Proliferation / drug effects
  • Cytokines / immunology
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Goblet Cells / drug effects
  • Interleukin-13 / metabolism
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mucin 5AC / metabolism
  • Mucus / metabolism
  • Neuroendocrine Cells / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism

Substances

  • Anti-Asthmatic Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Interleukin-13
  • Muc5ac protein, mouse
  • Mucin 5AC
  • Receptors, GABA-A
  • pingchuan yiqi