Transforming Growth Factor Beta/Smad3/GATA3 Axis Mediates the Therapeutic Effect of Ephedra sinica Stapf Polysaccharide in Allergic Rhinitis

Abstract Allergic rhinitis (AR) is a prevalent inflammatory disorder with limited therapeutic options. Ephedra sinica Stapf (ESP), a traditional Chinese herb, has shown potential in respiratory diseases, but its bioactive components and mechanisms remain unclear. This study investigates the anti-inflammatory effects of ESP-B4, a key ESP-derived compound, in an AR rat model and explores its underlying molecular mechanisms to support novel drug development. An AR rat model was established via ovalbumin (OVA) sensitization. Transcriptome sequencing identified differentially expressed genes associated with ESP-B4 treatment. Nasal mucosal pathology was evaluated using hematoxylin-eosin (HE) staining. The expression levels of TGF-β, Smad3, GATA3, and inflammatory cytokines (IL-5, TNF-α) were measured via RT-qPCR and Western blot. Co-immunoprecipitation (Co-IP) was used to assess Smad3-GATA3 protein interactions. ESP-B4 significantly alleviated AR symptoms, reducing sneezing and nasal scratching frequency. HE staining confirmed improved nasal mucosal integrity with reduced epithelial damage and edema. Mechanistically, ESP-B4 downregulated TGF-β, Smad3, and GATA3 expression while disrupting their protein-protein interaction, leading to suppressed IL-5 and TNF-α levels. ESP-B4 exerts potent anti-inflammatory effects in AR by inhibiting the TGF-β/Smad3/GATA3 signaling axis. These findings highlight its potential as a novel therapeutic agent for AR and provide a scientific basis for further drug development.