Acacetin Alleviates Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease in Mice by Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

Abstract

Acacetin, a flavonoid, exhibits potent anti-inflammatory activity. However, its therapeutic potential against cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, we aimed to investigate the protective role of acacetin in CS-induced COPD. A COPD mouse model was established by CS exposure. Mice were intragastrically administered with acacetin (20, 40, or 80 mg/kg). BEAS-2B cells were cultured with cigarette smoke extract (CSE) to explore the molecular mechanisms of acacetin. The effects of acacetin on lung function were evaluated using pulmonary function tests and histological staining. Its anti-inflammatory effects were assessed by immunohistochemistry, immunofluorescence, Western blotting, quantitative real-time PCR (qRT-PCR), and enzyme-linked immunosorbent assay. Acacetin ameliorated CS-induced lung function impairment, airway remodeling, and collagen deposition in mouse lungs. The levels of inflammatory factors decreased after acacetin treatment. Acacetin significantly reduced pyroptosis by inhibiting NLR family pyrin domain containing 3 (NLRP3) inflammasome-related protein expression in tissues and cells. Excessive lactate dehydrogenase (LDH) release induced by CSE was reversed by acacetin. Furthermore, NLRP3 overexpression in BEAS-2B cells reversed the suppressive effects of acacetin on inflammatory factor levels. Acacetin significantly alleviated CS-induced pyroptosis by modulating the NLRP3 inflammasome.