Comparative evaluation of three traditional herbal formulas on gastrointestinal motility in a mouse model of cold stress-induced dyspepsia

Abstract

BACKGROUND Cold exposure has traditionally been considered a pathological factor that can easily impair gastrointestinal (GI) digestion. Shihosogan-tang (ST), Yijung-tang (YT), and Pyeongwi-san (PS) are well-known herbal formulas frequently used to treat GI disorders in East Asia. AIM To compare the effects of these herbal formulas on GI motility and investigate their mechanisms of action using a cold stress (CS)-induced dyspepsia mouse model. METHODS C57BL/6J mice were exposed to CS by immersion in cold water (10 ± 1 °C) while being restrained in conical tubes for 1 hour. This procedure was repeated six times over 2 weeks. Herbal formulas or mosapride (positive control) were administered orally five times per week over a 2-week period. RESULTS The pre-test results revealed that CS, rather than restraint stress, significantly delayed gut motility in mice. However, PS and ST notably improved gastric emptying and intestinal transit, surpassing YT. Additionally, PS and ST significantly reduced gastric potential of hydrogen and increased pepsin and lipase gene expression compared to CS. The observed mechanisms likely involved increased gastric acidity and enhanced levels of digestive enzymes, such as pepsin and lipase. Furthermore, PS administration elevated GI hormone levels and metabolites related to the gut microbiota (5-hydroxytryptamine and short-chain fatty acid) more effectively than ST and YT treatments. CONCLUSION PS more effectively alleviated CS-induced GI dysfunction than both YT and ST. These comparative findings offer valuable insights for clinical applications in the treatment of cold-related digestive disorders. © 2025 Elsevier B.V., All rights reserved.