Protocatechuic acid alleviates chronic obstructive pulmonary disease model by reducing inflammation and oxidative stress via the AHR/CYP1A1/CYP1A2 pathway

Gen Physiol Biophys. 2025 Jul;44(4):303-315. doi: 10.4149/gpb_2025013.

Abstract

This study aimed to investigate the protective effects of protocatechuic acid (PCA), a natural phenolic acid, on a chronic obstructive pulmonary disease (COPD) model. The COPD mouse model was induced through cigarette smoke (CS) exposure, followed by administration of dexamethasone or PCA during modeling. Human bronchial epithelial (HBE) cells were stimulated with CS extract and treated with or without PCA (40 μM) and/or the aryl hydrocarbon receptor (AHR) activator FICZ (20 nM). Model mice exhibited significant weight loss, impaired lung function, and severe lung injury. Moreover, CS exposure promoted inflammation and oxidative stress and activated the AHR/CYP1A1/CYP1A2 pathway in mice. PCA significantly alleviated COPD symptoms by inhibiting inflammation, oxidative stress, and the AHR/CYP1A1/CYP1A2 pathway. CS extract-stimulated HBE cells exhibited decreased cell viability, increased inflammatory response and oxidative stress, and upregulation of AHR/CYP1A1/CYP1A2 pathway. These effects were reversed by PCA, but FICZ inhibited the protective effects of PCA on HBE cells. In conclusion, PCA improves COPD model by reducing inflammation and oxidative stress through inhibition of the AHR/CYP1A1/CYP1A2 pathway.

MeSH terms

  • Animals
  • Cell Line
  • Cytochrome P-450 CYP1A1* / metabolism
  • Disease Models, Animal
  • Humans
  • Hydroxybenzoates* / administration & dosage
  • Hydroxybenzoates* / pharmacology
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress* / drug effects
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / pathology
  • Receptors, Aryl Hydrocarbon* / metabolism
  • Signal Transduction / drug effects

Substances

  • protocatechuic acid
  • Receptors, Aryl Hydrocarbon
  • Hydroxybenzoates
  • Cytochrome P-450 CYP1A1