Quanzhen Yiqi decoction attenuates inflammation in mice with smoking-induced COPD by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome

J Pharm Pharmacol. 2025 Jan 6;77(1):95-110. doi: 10.1093/jpp/rgae047.

Abstract

Objective: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease.

Methods: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1β/IL-18.

Results: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1β and IL-18.

Conclusion: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.

Keywords: Nrf2; QZYQ; chronic obstructive pulmonary disease; cigarette smoke; inflammation; oxidative stress; the NLRP3 inflammasome.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Heme Oxygenase-1* / metabolism
  • Inflammasomes* / drug effects
  • Inflammasomes* / metabolism
  • Inflammation / drug therapy
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Oxidative Stress / drug effects
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Signal Transduction / drug effects
  • Smoking / adverse effects

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NF-E2-Related Factor 2
  • Drugs, Chinese Herbal
  • Inflammasomes
  • Nlrp3 protein, mouse
  • Nfe2l2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Membrane Proteins
  • Anti-Inflammatory Agents