Achalasia, a primary motility disorder of the esophagus, is characterized by impaired relaxation of the lower esophageal sphincter (LES), resulting in symptoms such as difficulty swallowing, regurgitation, chest discomfort, and weight loss. Standard pharmacological treatments, including calcium channel blockers and nitrates, often provide limited benefit, highlighting the need for alternative therapeutic strategies. This study explores the effects of Coptis chinensis and its major bioactive constituent, berberine, on LES relaxation, aiming to identify new avenues for treatment. The relaxation effects of C. chinensis extract and berberine were tested on LES pre-contracted with carbachol, across varying concentrations. To uncover the mechanisms driving berberine-induced relaxation, several pharmacological inhibitors were applied, including tetrodotoxin, ω-conotoxin GVIA, rolipram, vardenafil, KT5823, KT5720, NG-nitro-L-arginine, tetraethylammonium (TEA), apamin, iberiotoxin, and glibenclamide.
Both C. chinensis extract and berberine produced robust, concentration-dependent relaxation of the LES. The effect of berberine was notably attenuated by TEA, suggesting that activation of potassium channels is a key mechanism underlying its action. The findings indicate that C. chinensis and berberine facilitate LES relaxation, primarily through potassium channel modulation. These results support the potential of these compounds as therapeutic agents for esophageal motility disorders, such as achalasia.
