Auraptene Mitigates Cigarette Smoke and Lipopolysaccharide-Induced Chronic Obstructive Pulmonary Disease in Mice and BEAS-2B Cells via Regulating Keap1/Nrf2/HO-1 Pathway

Chronic obstructive pulmonary disease (COPD) is a most common respiratory condition characterized by airflow limitation, airway inflammation, and lung injury. The present study was undertaken to unveil the therapeutic potentials of the auroptene against lipopolysaccharide (LPS) and cigarette smoke (CS)-induced COPD in mice. The CS along with LPS was exposed to healthy C57BL/6 mice through the intranasal route to induce COPD. The exposure to CS was continued for 12 weeks. The LPS challenge was occurred on weeks 2, 4, 6, and 8. The auraptene was treated orally by gavage route 1 h before to CS exposure for last 4 weeks. After the completion of treatment, the respiratory function was assessed using a pulmonary function test equipment. The levels of mucin proteins, extracellular matrix (ECM) proteins, proliferative cytokine markers, epithelial marker protein E-cadherin, oxidative stress-related biomarkers, and inflammation-associated markers were assessed using respective commercial assay kits. An analysis of histopathology and histo-morphology was conducted on the pulmonary tissues. An in vitro assays were conducted on the CS condensate (CSC) and LPS-challenged BEAS-2B cells. The expressions of Keap1/Nrf2/HO-1 pathway associated proteins were assessed using assay kits. The findings of the current work has clearly proved that auraptene at 25 mg/kg concentrations significantly increased the pulmonary functions in the mice with COPD. The treatment of auraptene effectively reduced the ECM protein levels, proliferative cytokine marker levels, and inflammation-related cytokine levels in the COPD mice. In addition, the auraptene treatment effectively increased the antioxidants and mitigated the lung tissue injuries in the COPD mice. The Keap1/Nrf2/HO-1 signaling pathway expressions successfully regulated by the auraptene treatment in the CSC and LPS-induced BEAS-2B cells. Therefore, the current findings has highlighted that auraptene has the capability to be a beneficial intervention to treat COPD.