The Traditional Medicine Gamisoyosan Mitigates IBS Symptoms by Regulating Inflammatory and Pain Mechanisms

Background Gamisoyosan (GSS) is a traditional herbal medicine composed of nine medicinal ingredients and has been widely used for the treatment of various diseases, including gastrointestinal disorders. However, its therapeutic effects on irritable bowel syndrome (IBS) and the underlying mechanisms remain incompletely understood. Purpose This study aimed to evaluate the efficacy of GSS in alleviating symptoms in a zymosan-induced animal model of IBS and to elucidate its potential mechanisms, with a focus on inflammation, visceral pain, and ion channel modulation. Materials and Methods Zymosan-induced colitis and IBS-like symptoms were observed in male mice. The effects of GSS were evaluated by assessing colon length and weight, stool condition, histological changes, and tumor necrosis factor-alpha (TNF-α) levels. Pain-related behaviors were examined on days 1, 6, and 12. In addition, electrophysiological recordings in HEK293T cells expressing transient receptor potential (TRP) and voltage-gated sodium (NaV) channels were performed to assess the effects of GSS on ion channel activity. Results GSS significantly improved colon length, reduced colon weight, and normalized stool condition in zymosan-induced IBS mice, with effects comparable to sulfasalazine and amitriptyline. GSS prevented body weight loss and reduced colon inflammation by decreasing wall thickness and TNF-α levels. Pain-related behaviors were markedly alleviated and persisted up to day 12. Electrophysiological analyses showed that GSS enhanced TRPV1 and TRPV4 currents, inhibited TRPA1 activity, and dose-dependently suppressed NaV1.5 and NaV1.7 currents. Conclusion These findings suggest that GSS effectively alleviates IBS symptoms by attenuating intestinal inflammation and visceral pain. The therapeutic effects of GSS appear to be mediated, at least in part, through the modulation of TRP and NaV channels, supporting its potential as a multi-target treatment for IBS.