The mechanism of Qing-Fei-Yin decoction against influenza: Synergistical inhibition on viral replication and inflammation.

Abstract

BACKGROUND: Qing-Fei-Yin Decoction (QFY), derived from the classical formula Ma-Xing-Shi-Gan Decoction, emphasized "clearing heat and detoxifying, ventilating the lungs, and relieving cough," has been widely used for the treatment of influenza and has demonstrated significant efficacy. However, the studies on its mechanism were limited. OBJECTIVE: This study aimed to systematically evaluate its efficacy and explore its action mechanism using murine model of influenza. METHODS: The chemical profile of QFY was analyzed using UPLC-MS. A murine model challenged by PR8 (H1N1) influenza virus was established with C57BL/6J mice. Mice were randomly assigned to QFY-treat, oseltamivir-treat, PBS-treat, control groups. Multiple indicators (including survival rate, pathological alteration of lungs and colon, viral load, and inflammatory cytokine levels in lung and serum) were assessed. In addition, transcriptomic sequencing of lung tissues and 16S rRNA sequencing of gut microbiota were conducted. RESULTS: QFY improved the 14-day survival rate of infected mice from 0 % (PBS group) to 40 %, though still below the 60 % observed in the oseltamivir group. It alleviated lung pathological injury, reduced viral load, and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ, CCL2, CXCL10). Transcriptomic analysis of lung tissue revealed that QFY markedly suppressed the activation of NF-κB, TNF, IL-17, and NOD-like receptor signaling pathways, while enhancing the expression of genes related to epithelial barrier function. Furthermore, QFY restored gut microbiota homeostasis, increasing beneficial microbiota such as Barnesiella, which promotes short-chain fatty acid production, while inhibiting the overgrowth of pathogenic genera like Escherichia. CONCLUSION: QFY Decoction exhibited experimentally validated anti-influenza activity, mediated primarily through three mechanisms: inhibition of viral replication, suppression of excessive inflammation, and modulation of intestinal microbiota balance.