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

通过抑制NF-κB/MAPK信号通路,深入探究龙牙草提取物在卵清蛋白和脂多糖诱导的呼吸道炎症模型中发挥抗炎和肺保护作用的机制

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作者:Yeong-Geun Lee,Jeong Eun Kwon,Dae Won Park,Hae Rim Lee,Jinhyuk Lee,Yong-Min Choi,Eun-Ji Cho,Se Chan Kang

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. Agrimonia pilosa (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. In vivo, 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.

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