IMPACT OF CHAIHU SHUGAN SAN ON ESOPHAGEAL MUCOSAL HEALING AND 5-HT SIGNALING PATHWAY IN RATS WITH REFLUX ESOPHAGITIS: IMPLICATIONS FOR SPORTS NUTRITION AND RECOVERY

Abstract

Objective: To evaluate the effects of Chaihu Shugan San (ChSgS) on esophageal mucosal injury and the 5-HT signaling pathway in rats with reflux esophagitis (RE). Methods: Male Sprague-Dawley rats were divided into six groups: normal control, RE model, low-dose ChSgS (6.62 g/kg), high-dose ChSgS (13.23 g/kg), 5-HT receptor inhibitor (GR113808, 1.0 mg/kg), and a combined ChSgS + GR113808 group. RE was induced by partial pyloric ligation and tail clamping. Treatments were administered daily for 14 days. Esophageal pH, mucosal injury scores, inflammatory markers (5-HT, IL-8), and 5-HT pathway protein expressions were measured using ELISA, immunofluorescence, and western blotting. Results: The RE model group showed severe mucosal damage, elevated 5-HT, IL-8, and SERT protein levels, and decreased esophageal pH, 5-HT4R expression, and Ca²⁺ concentration. ChSgS treatment reduced mucosal damage, restored esophageal pH, and normalized protein levels in a dose-dependent manner. The GR113808 group experienced worse mucosal damage, while the combined ChSgS + GR113808 group showed partial improvement. Conclusion: ChSgS alleviates RE-induced esophageal injury by reducing SERT expression and activating the 5-HT4R/AC/PKA/Ca²⁺ pathway, suggesting its therapeutic potential for gastrointestinal health management.