Matrine Attenuates Mitochondrial Fragmentation in Ovalbumin-Induced Asthmatic Mice by Activating the AMPK/Nrf2 Pathway

Abstract

Background: Asthma, a prevalent respiratory condition, is characterized by hyperresponsiveness and airway inflammation, and mitochondrial dysfunction and inflammation can exacerbate these symptoms. Therefore, this study aims to investigate whether matrine, known for its anti-inflammatory properties, attenuates mitochondrial fragmentation in asthmatic mice by activating the adenosine 5′-monophosphate-activated protein kinase (AMPK)/Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) pathway. Methods: An asthma model was induced in BALB/c mice through sensitization with ovalbumin (OVA). The mice were given matrine (50 mg/kg, 100 mg/kg) and dexamethasone (2 mg/kg) through gavage feeding. Serum, lung tissue, and bronchoalveolar lavage fluid (BALF) were collected. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blot analyses were used to assess changes in inflammation and oxidative stress levels in the airways and lung tissues. Furthermore, the expression levels of AMPK-dynamin-related protein 1 (DRP1)-NOD-like receptor family, pyrin-domain-containing-3 (NLRP3) pathway proteins were evaluated in the lung tissues. Results: Matrine treatment significantly reduced airway inflammation and mucus secretion in OVA-induced asthmatic mice (p < 0.05). Notably, inflammatory cell infiltration around the airway and mucus secretion in the airway, as evidenced by H&E and PAS staining, was substantially decreased in matrine-treated mice compared to the OVA group. Additionally, matrine significantly reduced T-helper cell type 2 (Th2) cytokine levels in mediastinal lymph nodes and BALF, as well as serum immunoglobulin (Ig)E levels (p < 0.05). Moreover, matrine exhibited antioxidant effects by enhancing superoxide dismutase (SOD) and catalase (CAT) activity while reducing malondialdehyde (MDA) expression and reactive oxygen species (ROS) accumulation in lung tissues (p < 0.05). Furthermore, the suppression of Caspase-1, NLRP3, and interleukin (IL)-1β by matrine indicated its anti-inflammatory properties (p < 0.05). Mechanistically, matrine increased AMPK phosphorylation, inhibited DRP1-mediated mitochondrial fission, and promoted mitochondrial fusion, suggesting its potential to alleviate airway inflammation (p < 0.05). Conclusions: Matrine alleviates allergic airway inflammation in OVA-induced asthmatic mice by regulating the AMPK-DRP1-NLRP3 pathway.