Shenling Tongqiao powder targets TGF-β1/Smad-Wnt/β-catenin axis to suppress epithelial-mesenchymal transition in chronic rhinosinusitis.

BACKGROUND

Chronic rhinosinusitis (CRS), a prevalent upper respiratory inflammatory disorder, remains challenging in clinical management due to the high recurrence rates. Traditional Chinese Medicine (TCM) pathogenesis theory posits that CRS primarily stems from deficiency syndromes involving pulmonary and splenic dysfunction. Shenling Tongqiao Powder (SLTQP), a formulated herbal preparation, has demonstrated clinical efficacy in enhancing pulmonary-splenic function and CRS symptom alleviation. But its underlying pharmacological mechanisms require systematic elucidation.

METHODS

Nasal mucosa of nasal septum deviation and CRS without nasal polyp (CRSsNP) patients were collected for histopathological analysis in epithelial-mesenchymal transition (EMT). The rat model of CRS was established using Staphylococcus aureus while the body weight, the number of nose-scratching and sneezing were recorded. Sinus inflammation was evaluated by computed tomography (CT) scanning. Histopathological staining, Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) and western blot were applied for assessment of TGF-β1/Smad and Wnt/β-catenin signaling and EMT in rat and cell model. Inflammatory factors of rat nasal lavage solution and serum were analyzed by ELISA. LC-MS/MS was used for analysis of SLTQP decoction and pharmaceutic serum. The energy between these molecules and TGF-β1/Smad and Wnt/β-catenin was calculated by molecular docking, the direct binding affinity was confirmed and quantified via surface plasmon resonance (SPR).

RESULTS

Histopathological analysis revealed marked EMT elevation in nasal mucosa specimens from CRSsNP patients. SLTQP administration significantly attenuated EMT progression and suppressed nasal inflammatory responses in CRS rat models, likely mediated via concurrent inhibition of TGF-β1/Smad and Wnt/β-catenin signaling cascades. Phytochemical profiling via liquid chromatography-mass spectrometry (LC-MS) characterized both the native SLTQP decoction components and their bioactive metabolites in systemic circulation. Notably, molecular docking analyses predicted and SPR confirmed strong binding affinities between these identified compounds and critical regulatory nodes within TGF-β1/Smad and Wnt/β-catenin, suggesting a potential multi-target therapeutic mechanism.

CONCLUSIONS

Our integrated approaches firstly documented EMT dysregulation by multiple makers in CRSsNP patients, and provided novel insights into SLTQP's anti-EMT effects through dual pathway modulation, supporting its application as a complementary CRS treatment strategy.