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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Comparative evaluation of three traditional herbal formulas on gastrointestinal motility in a mouse model of cold stress-induced dyspepsia
Jing-Hua Wang, Song-Yi Han, Liangliang Wu, Uijeong Han, Si-Kyung Cho, Chan-Woong Park, Young-Won Chin, Mi Young Lim, Hojun Kim
Jing-Hua Wang, Institute of Oriental Medicine, Dongguk University, Goyang 10326, South Korea
Song-Yi Han, Liangliang Wu, Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang 10326, South Korea
Uijeong Han, Si-Kyung Cho, Department of Biological and Environmental Science, Dongguk University, Goyang 10326, South Korea
Chan-Woong Park, Young-Won Chin, Natural Product Research Institute and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South Korea
Mi Young Lim, Precision Nutrition Research Group, Korea Food Research Institute, Wanju 55365, South Korea
Hojun Kim, Division of Rehabilitation Medicine of Korean Medicine, Department of Oriental Rehabilitation Medicine, Dongguk University, Ilsan Hospital, Goyang 10326, South Korea
Author contributions: Wang JH contributed to writing the original draft, methodology, formal analysis, and data curation; Han SY and Cho SK contributed to validation, methodology, data curation; Wu L contributed to methodology, formal analysis; Han U contributed to formal analysis and data curation; Park CW contributed to visualization, validation; Chin YW contributed to validation, formal analysis; Lim MY contributed to writing-review and editing; Kim H contributed to writing-review and editing, supervision, project administration, funding acquisition, conceptualization.
Supported by the National Research Foundation of Korea, No. 2022M3A9E4017033.
Institutional animal care and use committee statement: The animal experimental protocol was approved by the Institutional Animal Ethics Committee of Dongguk University (No. IACUC-2024-03260; approval date: 8 April 2024).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hojun Kim, PhD, Professor, Division of Rehabilitation Medicine of Korean Medicine, Department of Oriental Rehabilitation Medicine, Dongguk University, Ilsan Hospital, 27 Dongguk-ro, Goyang 10326, South Korea.
kimklar@dongguk.ac.kr
Received: May 23, 2025
Revised: June 24, 2025
Accepted: August 15, 2025
Published online: September 21, 2025
Processing time: 119 Days and 9.1 Hours
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.
Core Tip: This study systematically compared the therapeutic effects of three classical herbal formulas [Pyeongwi-san (PS), Shihosogan-tang, and Yijung-tang] in a mouse model of cold stress-induced dyspepsia. Among them, PS was the most effective in restoring gastrointestinal motility, enhancing gastric acid secretion and upregulating digestive enzymes gene expression, and modulating serotonin, short-chain fatty acids, bile acid receptors, and glucagon-like peptide-1 signaling. These findings elucidate the mechanisms of PS’s superior efficacy and strongly support its clinical application in treating cold-induced gastrointestinal dysfunction.
