Piperine attenuates production of inflammatory biomarkers, oxidative stress and neutrophils in lungs of cigarette smoke-exposed experimental mice

Abstract

Cigarette smoking (CS) induced chronic obstructive pulmonary disease (COPD) is third leading cause of global pulmonary health issue. Currently, there is no effective therapeutic strategy to control perpetuating inflammatory response in COPD. The aim of current study was to investigate the protective effects of piperine in CS-induced murine model of COPD. Exposure of experimental animals to cigarettes smoke twice daily for 10 weeks resulted in increased production of pro-inflammatory mediators including IL-1β, IL-8, TNF-α, LTB-4 and neutrophil elastase (NE) in bronchoalveolar (BAL) fluid. Oxidative stress biomarkers, malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide and MMP9 also significantly increased in CS-control mice lungs as compared to normal control group (P < 0.001). Moreover, CS also increased recruitment of inflammatory cells, neutrophils and macrophages into BAL fluid and altered breathing rate and tidal volume as compared to normal control mice. However, oral treatment of CS-exposed animals with test drug, piperine (10 mg/kg, b.w. or 20 mg/kg, b.w.) or reference standard methyl prednisolone (3.25 mg/kg, b.w.) for 21 days or 7 days, respectively, significantly (p < 0.05, 0.01, 0.001) improved pulmonary function and reversed CS-induced production of cytokines, oxidative stress biomarkers and other biochemicals as compared to CS-exposed control mice. Further, In silico molecular docking studies exhibited attractive binding affinity of piperine for human neutrophil elastase, MMP-9, MPO and IL-8 receptors. Findings of our study suggest protective effect of piperine in experimental animals by repressing CS-induced infiltration of inflammatory cells and thereby exaggerated production of pro-inflammatory mediators and oxidative stress.