@Article{biocell.2025.066223,
AUTHOR = {Yan-Jyun Lin, I-Ta Lee, Wen-Bin Wu, Chien-Chung Yang, Chiang-Wen Lee, Fuu-Jen Tsai, Hui-Ching Tseng, Wei-Ning Lin, Li-Der Hsiao, Chuen-Mao Yang},
TITLE = {Targeting c-Src/PKC<b>α</b>/MAPK/NF-<b>κ</b>B: Salvianolic Acid A as a Protective Agent against Silica Nanoparticle-Induced Lung Inflammation},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {7},
PAGES = {1265--1290},
URL = {http://www.techscience.com/biocell/v49n7/63105},
ISSN = {1667-5746},
ABSTRACT = { <b>Background:</b> Silica nanoparticles (SiNPs), commonly utilized in industrial and biomedical fields, are known to provoke pulmonary inflammation by elevating cyclooxygenase-2 (COX-2) levels in human pulmonary alveolar epithelial cells (HPAEpiCs). Salvianolic acid A (SAA), a water-soluble polyphenol extracted from <i>Salvia miltiorrhiza</i> (Danshen), possesses well-documented antioxidant and anti-inflammatory activities. Nevertheless, its potential to counteract SiNP-induced inflammatory responses in the lung has not been thoroughly explored. <b>Objective:</b> This study aimed to evaluate the protective role and mechanistic actions of SAA against SiNP-triggered inflammation in both cellular and animal models. <b>Methods:</b> HPAEpiCs were pre-incubated with SAA prior to SiNP exposure to investigate changes in COX-2 expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) secretion. A murine model of SiNP-induced lung inflammation was used for <i>in vivo</i> validation. Key inflammatory signaling proteins, including c-Src, PKCα, p42/p44 MAPK, and NF-κB p65, were analyzed for phosphorylation status. NF-κB promoter activity was also assessed. Pharmacological inhibitors and siRNA-mediated silencing were employed to verify the signaling cascade responsible for COX-2 regulation. <b>Results:</b> SAA treatment markedly suppressed SiNP-induced upregulation of COX-2 and PGE<sub>2</sub> in both HPAEpiCs and mouse lung tissues. SAA also reduced the activation (phosphorylation) of c-Src, PKCα, p42/p44 MAPK, and NF-κB p65, alongside diminishing NF-κB transcriptional activity. Functional studies using inhibitors and gene silencing further supported the involvement of these pathways in mediating the observed anti-inflammatory effect. <b>Conclusion:</b> By concurrently targeting several upstream pro-inflammatory signaling pathways, SAA demonstrates robust potential in alleviating SiNP-induced lung inflammation. These results highlight SAA as a promising candidate for therapeutic intervention in environmentally triggered respiratory conditions.},
DOI = {10.32604/biocell.2025.066223}
}