Abstract
To Editor
Functional gastrointestinal disorders (FGIDs) have become a widespread global health challenge, affecting about 10% of the world's population. 1 The pathogenesis of these diseases is complex, involving gastrointestinal motility disorders, visceral hypersensitivity, brain-gut axis disorders and other factors. 2 Although modern medicine has proposed a variety of treatment strategies, including diet adjustment, antidepressants and prokinetic drugs, it is still difficult for most patients to obtain satisfactory curative effect. 3 In recent years, the traditional Chinese medicine (TCM) compound with its overall concept and multi-target regulatory effect has provided new ideas for the treatment of FGIDs. 4
Recently, the World Journal of Gastroenterology published a study by Wang et al entitled “ Comparative evaluation of three traditional herbal formulas on gastrointestinal motility in a mouse model of cold stress-induced dyspepsia “ offers valuable insights. This study explored the effects of three classical Chinese herbal formulas on gastrointestinal motility and related mechanisms in a mouse model of cold stress-induced dyspepsia.
These findings hold important clinical implications and provide a new idea for the application of TCM in the treatment of FGIDs.
Background
Cold stress is a common cause of functional gastrointestinal disorders (FGIDs), impacting digestive function through multiple mechanisms. These mechanisms include alterations in gastrointestinal motility, gastric acid secretion, and gut microbiota composition. 5 Specifically, Cold stress can specifically slow gastrointestinal peristalsis, impeding normal food passage and leading to food retention in the stomach, which results in bloating and discomfort. 6 It can also dysregulate gastric acid secretion, leading to either excessive secretion that irritates the gastric mucosa or insufficient secretion that impairs food digestion and absorption. Furthermore, cold stress can modify the composition and metabolic activity of gut microbiota, compromise intestinal barrier function, and increase intestinal inflammation. 7
According to TCM theory, cold stress may lead to spleen and stomach deficiency and cold, which can affect digestive function and cause symptoms such as bloating and abdominal pain. 5 TCM treatment strategies typically focus on warming the middle and dispersing cold, as well as strengthening the spleen and stomach to restore and regulate gastrointestinal function. In addition to the TCM formulas discussed in the study, other remedies such as Lizhong Wan, Fuzi Lizhong Wan, and Xiangsha Liujunzi Tang can also be effectively used to manage digestive disorders8–10 (Figure 1). TCM has shown significant advantages in terms of toxic side effects. Compared to chemical drugs, most TCM have less damage to liver and kidney function, milder gastrointestinal reactions, and relatively lower risk of cardiac toxicity. 11 This characteristic makes TCM safer and more tolerable in long-term treatment or chronic disease management. In addition, the multi-target and multi pathway mechanism of action of TCM provides broad prospects for its application in the treatment of complex diseases.
Traditional chinese medicine as a potential therapy for relieving functional gastrointestinal disorders. Functional gastrointestinal diseases can be triggered by cold exposure stimulation, leading to weakened gastrointestinal motility, affected gastric acid secretion, decreased digestive enzyme activity, and imbalanced gut microbiota. The signaling pathways involved may include the HPA axis and intestinal inflammatory pathways such as nuclear transcription factor-kappa B (NF-κB). Future research can be based on the “disease-Targets-Drug” interaction network, utilizing modern technologies such as network pharmacology and metabolomics to elucidate the mechanism of multi-component and multi-target synergistic effects. The integration of traditional Chinese and Western medicine can also accelerate its modernization and clinical application.
Strengths and Limitations
The three TCM formulas examined in this study，including Chaihu Shugan Tang (ST), Lizhong Tang (YT), and Pingwei San (PS), demonstrated significant improvements in gastrointestinal function. The compositions of Shihosogan-tang (ST) (Chai-Hu-Shu-Gan-Tang), Yijung-tang (YT) (Li-Zhong-Tang), and Pyeongwi-san (PS) (Ping-Wei-San) were list in Table 1. These formulas not only enhanced gastric emptying and intestinal transit but also regulated gastric acid secretion, boosted digestive enzyme gene expression, promoted intestinal 5-hydroxytryptamine (5-HT) secretion, modulated short-chain fatty acid (SCFA) levels, and inhibited inflammatory factor expression. Notably, their regulatory effects on bile acid receptor gene expression underscore the multi-target and multi-pathway synergistic actions characteristic of TCM formulas. These findings provide a modern scientific basis for the traditional medical concept of “warming the stomach and dispelling coldness.”
The Compositions of Shihosogan-Tang (ST), Yijung-Tang (YT), and Pyeongwi-san (PS).
However, this study has several limitations. The sample size was relatively small, and only a single dose of the TCM formulas was tested, precluding evaluation of dose-response relationships. Future research should expand the sample size to include both male and female mice and explore efficacy and safety across different doses. Current research on TCM for functional gastrointestinal disorders (FGIDs) is in its early stages and faces several challenges. Most studies focus on clinical efficacy without in-depth mechanistic exploration. The pharmacological effects of herbal compounds involve multiple targets and pathways, necessitating analysis of herbal components in the blood to elucidate their metabolic processes. 12 Network pharmacology could also be employed to identify targets of herbal formulas in FGID treatment. 13 There is no integrated use of network toxicology to help identify targets and pathways related to toxicity in evaluating the toxicity of traditional Chinese medicine. Lack of comprehensive pharmacokinetic data is crucial for understanding the absorption, distribution, metabolism, and excretion of TCM. In addition, existing studies are often characterized by small sample sizes and short-term observations, lacking large-scale, multicenter, long-term clinical trials to verify safety and efficacy. The complex composition of TCM formulas and the lack of unified quality control standards further affect the reliability and reproducibility of research results. Standardize bioactive compounds using high-performance liquid chromatography (HPLC) and comprehensively analyze chemical components using mass spectrometry techniques such as LC-MS/MS.
Future Research Directions
Future research should focus on the following directions. Firstly, based on the “Disease-targets-drug” interaction network, combined with modern science and technology such as network pharmacology, metagenomics to deeply explore the mechanism underlying TCM compound therapy for FGIDs. This approach will help elucidate the multi-component and multi-target synergistic effects. Secondly, integrating TCM with Western medicine holds promise. 14 Western medicine can rapidly alleviate specific symptoms, such as using proton pump inhibitors (PPIs) to suppress gastric acid secretion and prokinetic agents to enhance gastrointestinal motility, while TCM can holistically regulate spleen and stomach function, improve patients’ physical condition and reduce recurrence rates. In the study of herb formulas, due to their complex characteristics of multiple components and targets, the action of a single compound is often difficult to fully explain the overall efficacy of the compound. However, the analysis of specific compounds is crucial for revealing the mechanism of action of traditional Chinese medicine formulas, which is also an important direction for future research. Moreover, high-quality clinical research is essential. This involves optimizing study designs, expanding sample sizes, and extending observation periods to gather more comprehensive and reliable clinical evidence (Figure 1).
In conclusion, TCM formulas offer broad potential for treating FGIDs. Further in-depth research is anticipated to fully realize the therapeutic potential of TCM and provide safer and more effective treatment options for patients with FGIDs.
Footnotes
Authors’ Contributions
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability
Not Applicable.