Baicalin Enhances Respiratory Mucosal Immunity by Modulating Antiviral Protein Expression and T-cell Homeostasis During H9N2 Infection

Zhenyi Liu¹Haotong Guo¹Yan Zhi¹Xiaorui Jiang²Qian Zhang^1*

• ¹Beijing University of Agriculture, Beijing, China
• ²Yantai Yuhuangding Hospital, Yantai, Shandong Province, China

The H9N2 avian influenza virus, although not highly pathogenic, still poses ongoing risks to poultry health and food security due to its ability to resist vaccines and its potential to spread to humans. This study looks at how baicalin, a flavonoid from Scutellaria baicalensis, helps improve respiratory mucosal immunity against H9N2 infection. Baicalin targets alveolar epithelial cells (MLE-12), which are important for mucosal defense. It increases antiviral proteins Mx1 and PKR in a way that depends on both dose and time, helping to counteract the virus's suppression of these defense proteins. In addition to strengthening this epithelial barrier, baicalin has both antiviral and immune-regulating effects: it directly blocks viral replication and helps restore the CD4+/CD8+ T cell ratio in H9N2-infected mice. Most importantly, baicalin reduces lung damage and spleen shrinkage while keeping the immune system balanced. These results show that baicalin enhances mucosal antiviral defenses by simultaneously regulating innate antiviral pathways (Mx1 and PKR) and restoring adaptive immune balance (CD4+/CD8+ T-cell ratio). These dual protective effects highlight baicalin's potential as a natural therapeutic strategy for improving mucosal immunity against vaccine-resistant influenza viruses such as H9N2, contributing valuable insights into plant-derived immunomodulatory approaches against emerging zoonotic viral threats.