Dual Effects of Sodium Houttuyfonate Against Acute Rhinosinusitis: Antibacterial Action and Epithelial Barrier Repair Through the p38 MAPK/ERK Pathway.

Background: Houttuynia cordata Thunb, a traditional medicinal herb, is the source of sodium houttuyfonate (SH), a stabilized derivative with antibacterial, antiviral, and anti-inflammatory activities. Acute rhinosinusitis (ARS) comprises viral, post-viral, and bacterial forms; bacterial ARS causes severe inflammation and epithelial barrier disruption. Despite wide clinical use, the mechanisms of SH in ARS remain unclear. Methods: Network pharmacology was applied to identify SH-associated targets and pathways. An ARS rat model was induced by inserting Staphylococcus aureus-soaked Merocel sponges into the nasal cavity. Rats received low, medium, or high doses of SH, with control and positive drug groups. Symptom scoring, CT, histopathology, hematology, ELISA, qRT-PCR, and immunohistochemistry were conducted. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with lipopolysaccharide (LPS) and treated with SH, with or without MAPK modulators SB203580 (inhibitor) or Anisomycin (activator). Cell viability, cytokine expression, and ERK/p38 MAPK phosphorylation were assessed. Results: SH improved nasal symptoms, reduced epithelial injury, and normalized nasal pH in ARS rats. It downregulated IL-1β, IL-6, TNF-α, and ICAM-1 while upregulating IL-4. Transmission electron microscopy showed restoration of ciliary and mitochondrial integrity. In HNEpCs, 60 μM SH was optimal by CCK-8 assay. In LPS-stimulated cells, SH suppressed IL-1β/IL-6 mRNA and inhibited ERK and p38 MAPK phosphorylation; these effects were reversed by Anisomycin, confirming pathway involvement. Conclusion: SH alleviates sinonasal inflammation in ARS by inhibiting bacterial activity and restoring epithelial integrity through p38 MAPK/ERK suppression. These findings support SH as a potential therapy for upper airway inflammatory diseases.