Boehmeria nivea (L.) Gaud. Ameliorates Oxidative stress-mediated Inflammatory Responses and Apoptosis in LPS/CSC-induced Chronic Obstructive Pulmonary Disease Mouse Model
Introduction: Boehmeria nivea (L.) Gaud. has traditionally been regarded as a functional food with applications in various inflammatory disorders. However, its role in chronic obstructive pulmonary disease (COPD) has not yet been clarified. Methods: In this study, the preventive efficacy of the ethyl acetate fraction of B. nivea (L.) Gaud. leaves (EA-BN) was evaluated in a COPD model established by intranasal instillation of lipopolysaccharide (LPS; 0.5 mg/kg body weight) and cigarette smoke condensate (CSC; 12.5 mg/kg body weight) in male C57BL/6N mice. The experimental groups received dexamethasone (3 mg/kg) as a positive control or EA-BN at doses of 200 mg/kg. Results: EA-BN administration significantly reduced T helper 1 cytokine levels and decreased macrophage and neutrophil counts in bronchoalveolar lavage fluid. Histological analyses revealed that EA-BN mitigated alveolar destruction and inflammatory infiltration, whereas pulmonary function tests demonstrated improvements in the FEV0.1/FVC ratio and lung elastance in the LPS/CSC-induced COPD. Additionally, EA-BN alleviated oxidative stress by promoting the nuclear translocation of Nrf2 and enhancing the expression of its downstream targets, HO-1 and NQO1, leading to a reduction in reactive oxygen species and nitric oxide production. EA-BN downregulated thioredoxin-interacting protein and NLRP3 inflammasome activation, thereby suppressing caspase-1 and IL-1ß expression, and also attenuated apoptosis by modulating the Bax/Bcl-2/caspase-3 pathway. Discussion: Collectively, these findings suggest that EA-BN possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, supporting its potential as a preventive agent against COPD. Overall design: This study investigated transcriptomic changes in lung tissue using an LPS/CSC-induced COPD mouse model and evaluated the effect of EA-BN treatment. Male C57BL/6N mice were assigned to three groups for RNA-seq analysis: Normal control (NC; PBS intranasal instillation with vehicle), COPD (LPS/CSC intranasal instillation with vehicle), and EA-BN-H (LPS/CSC intranasal instillation with EA-BN 200 mg/kg). LPS (0.5 mg/kg) and CSC (12.5 mg/kg) were intranasally instilled under light anesthesia on days 1, 6, and 13. EA-BN (200 mg/kg; in 2% DMSO) or vehicle was administered orally once daily from days 1 to 14. Lung tissues were collected on day 15, and total RNA was extracted using TRIzol reagent. RNA quality was assessed prior to library preparation, and RNA-seq was performed to compare gene expression profiles among NC, COPD, and EA-BN-H groups.