Yuye Jinhua Qingre Tablets Attenuate Acute Pharyngitis by inhibiting the Complement Cascade and C5a/C5aR1 Axis.

BACKGROUND: Acute pharyngitis (AP) is a common upper respiratory tract infection, primarily characterized by symptoms such as throat pain, redness, swelling, and difficulty swallowing. It is typically caused by viral infections, bacterial infections, or physical and chemical irritants. Yuye Jinhua Qingre Tablets (YYJH) are recognized for their ability to clear heat, detoxify, reduce swelling, and alleviate pain, making them a common treatment option for acute pharyngitis. However, research on their specific mechanisms of action is still inadequate. METHODS: Using UPLC-Q-Exactive-Orbitrap-MS technology combined with serum pharmacochemical analysis, the main chemical components and blood components of YYJH were identified. The anti-inflammatory activity was verified through the ammonia-induced acute pancreatitis (AP) model in SD rats and the LPS-stimulated NP69SV40T cell inflammation model. Integrating transcriptomics, proteomics, and bioinformatics analysis revealed the mechanism of YYJH in treating AP, which was further validated by molecular biology experiments. RESULTS: Twelve blood-entry components were identified, and their anti-inflammatory effects were validated using the SD rat acute pancreatitis (AP) model and the NP69SV40T cell inflammation model. The study results indicated that the drug significantly improved the pathological damage of the pharyngeal mucosa in rats with the AP model, reducing the levels of inflammatory cells in peripheral blood and serum inflammatory factors. The combined analysis of transcriptomics and Astral DIA proteomics revealed that the anti-inflammatory effects of YYJH are associated with the regulation of the classical complement pathway, characterized by the downregulation of complement components C1q, C3, C5, C9, and the modulation of macrophage infiltration and pro-inflammatory cytokine release through the C5a/C5aR1 axis. Gene set enrichment analysis further suggested that YYJH can alleviate AP-related metabolic disorders and immune dysregulation. Molecular biology experiments demonstrated that after YYJH intervention, the complement cascade reaction was significantly inhibited, with downregulated expression levels of C5a and C5aR1, and decreased membrane localization signals of the macrophage marker F4/80, along with reduced expression levels of inflammatory factors. CONCLUSIONS: Research indicates that YYJH exerts anti-inflammatory effects by regulating the classical complement pathway and the C5a/C5aR1 axis, inhibiting the production of inflammatory mediators and the activation of immune cells. This provides a theoretical basis for the molecular mechanisms underlying traditional Chinese medicine in the treatment of acute pharyngitis.