Abstract

Pharyngeal inflammation is a common upper respiratory tract disease characterized by increased inflammatory responses and mucin accumulation. Gentiopicroside (GPS), a natural compound with anti-inflammatory activity, has not been previously studied for its inhibitory effects on pharyngeal inflammation and its underlying mechanisms. This study aimed to investigate whether GPS inhibits pharyngeal inflammation in rats induced by Staphylococcus aureus ( S. aureus ) components and to elucidate the underlying mechanisms. In vivo, pharyngeal inflammation was induced in rats using S. aureus components, and GPS was administered to assess its effects on pharyngeal histopathological damage, mucosa injury, immune cell balance, secretory immunoglobulin A (SIgA) levels, cytokine production, and the expressions of E-cadherin, mucin5AC (MUC5AC), and cyclooxygenase-2 (COX-2). In vitro, human lung mucoepidermoid carcinoma cells (NCI-H292) were stimulated with lipoteichoic acid (LTA) to mimic S. aureus component-induced inflammatory stimulation. The effects of GPS on LTA-induced cytokine IL-1β and IL-6, COX-2, prostaglandin E2 (PGE2), MUC5AC, and E-cadherin expressions were evaluated. SiRNA against COX-2 was transfected, and a limited in vitro biochemical observation of GPS with recombinant MUC5AC was performed. GPS alleviated rat pharyngeal inflammation by improving pharyngeal histopathology, reducing mucosa injury, balancing immune cells, enhancing SIgA, and downregulating cytokines. It also inhibited the reduction of E-cadherin and the upregulation of MUC5AC and COX-2 in the rat pharynx and trachea. In NCI-H292 cells, GPS blocked LTA-induced increases in IL-1β, IL-6, COX-2, PGE2, and MUC5AC, as well as LTA-reduced E-cadherin. Transfection with siRNA against COX-2 further blocked LTA-induced MUC5AC expression, and GPS lost its inhibitory effect on MUC5AC expression, indicating that COX-2 was involved. Additionally, GPS showed a limited in vitro biochemical observation on recomb