Mechanistic insight into the anti-inflammatory and lung-protective effects ofextract via NF-κB/MAPK inhibition in ovalbumin- and lipopolysaccharide-induced respiratory inflammation models.

Abstract

CONTEXT: Asthma and COPD involve airway inflammation, oxidative stress, and epithelial cell apoptosis. While corticosteroids are common, long-term use can cause adverse effects, prompting interest in plant-based anti-inflammatory alternatives.(AP) shows promise, but its effectiveness in airway inflammation requires further study. OBJECTIVE: To assess anti-inflammatory and lung-protective effects in LPS-stimulated A549 cells and an OVA+LPS mouse model, focusing on NF-κB/MAPK pathways and apoptosis-related markers. MATERIALS AND METHODS: A549 cells were pretreated with AP and stimulated with LPS. Pro-inflammatory cytokine mRNA levels and phosphorylation of NF-κB p65, p38, ERK, JNK were measured., AP was given orally during OVA+LPS challenges. Cytokines and chemokines in bronchoalveolar lavage fluid (BALF), lung matrix metalloproteinases (MMP-1/9/12), Bax/Bcl-2 ratio, histopathological analysis, and systemic toxicity markers (AST, ALT, ALP, and BUN), body and organ weights, and gross examination were evaluated. RESULTS: In A549 cells, AP reduced LPS-induced pro-inflammatory mRNA and inhibited NF-κB p65 and MAPK phosphorylation. In the OVA+LPS model, oral AP lowered BALF levels of CXCL-1, CXCL-2, IL-1β, IL-6, and TNF-α, and downregulated lung MMP-1/9/12, reducing Bax/Bcl-2 ratio with histological improvements. At 100 mg/kg, CXCL-1 and CXCL-2 decreased to about 73.2% and 89.2%, respectively. IL-1β and IL-6 levels decreased by 72.5% and 37.4%, respectively, with IL-6 significant only at the high dose. No systemic toxicity was observed, with stable serum toxicity markers and no abnormal findings. DISCUSSION AND CONCLUSIONS: AP exhibits anti-inflammatory and lung-protective effects by inhibiting NF-κB/MAPK signaling and regulating proteolysis and apoptosis, indicating it as a safe, effective treatment for airway inflammation.