The experimental model at the heart of the study is known as water immersion and restraint stress, or WIRS, a widely used laboratory approach for inducing acute gastritis. In this model, mice are restrained and immersed in water, typically at ambient temperature, which produces a powerful psychological and physiological stress response. The stress cascade that follows is well documented in the literature: blood flow to the gastric mucosa is reduced, the protective mucus barrier is compromised, and inflammatory and oxidative pathways are activated. The result is hemorrhagic erosion of the stomach lining that closely mimics the kind of acute stress-induced gastric injury seen in clinical settings, from intensive care patients to individuals experiencing severe psychological strain. Because WIRS captures this multifactorial injury process, it is considered a demanding test bed for any candidate gastroprotective agent.

Before committing to a single formulation, the team ran an exploratory ratio-screening experiment, testing different proportions of ginseng extract to ginger extract. The 3:1 ginseng-to-ginger formulation stood out: it significantly reduced gastric hemorrhagic lesions relative to the stressed, untreated group. The authors are explicit that this selection was exploratory in nature. The 3:1 ratio was chosen because of its activity relative to the WIRS control group rather than through a formal demonstration of superiority over the other ratios tested. That distinction matters for how the findings should be interpreted, since the screening was designed to identify a representative active formulation for deeper investigation, not to crown a definitive optimal recipe. With the 3:1 formulation in hand, the researchers moved on to dose-ranging and mechanistic studies built around seven days of oral administration before the stress challenge.

The molecular results point to a coordinated dampening of inflammation. After the seven-day pretreatment, the 3:1 formulation significantly reduced the protein abundance of three key inflammatory mediators in gastric tissue: interleukin-1β, a potent pro-inflammatory cytokine central to mucosal inflammation; inducible nitric oxide synthase, the enzyme that floods tissue with nitric oxide during inflammatory responses; and cyclooxygenase-2, the inducible enzyme that drives prostaglandin production in inflamed tissue. All three were measured relative to stressed mice given distilled water instead of the formulation. Together, these reductions suggest that the ginseng-ginger combination acts, at least in part, by quieting the inflammatory signaling that amplifies stress-induced mucosal damage rather than merely coating or buffering the stomach lining.

Oxidative stress emerged as a second major axis of protection. The formulation reduced lipid peroxidation, the process by which reactive oxygen species attack the lipid membranes of cells, producing damaging byproducts that are a hallmark of oxidant injury in gastric tissue. At the same time, the treatment increased the activity of glutathione peroxidase, an endogenous antioxidant enzyme that uses glutathione to neutralize peroxides before they can accumulate. The paired findings, less lipid damage alongside stronger enzymatic antioxidant defense, are consistent with the interpretation that the formulation enhances the stomach’s intrinsic capacity to cope with the oxidative burst that accompanies severe stress. This dual action on inflammation and oxidation mirrors mechanisms previously attributed to ginsenosides in ginseng and gingerols in ginger, though the present study examined the combined formulation rather than isolating individual compounds.

One important negative result adds nuance to the story. The formulation did not significantly affect the mRNA expression of three receptors that govern gastric acid secretion: the M3 muscarinic receptor, the H2 histamine receptor, and the CCK2 receptor for gastrin and cholecystokinin. These receptors are the classic pharmacological targets of acid-suppressing drugs, from anticholinergics to H2 blockers and proton pump inhibitor pathways. However, the authors caution that mRNA findings alone are insufficient to evaluate actual gastric acid-secretory function, and because gastric acid secretion was not directly measured in the study, it remains unclear whether modulation of acid secretion contributed to the gastroprotective effects at all. In other words, the protection observed appears to operate through anti-inflammatory and antioxidant routes, with any acid-related contribution remaining an open question for future work.

The study’s histological observations, presented as supportive qualitative material, included hematoxylin and eosin stained gastric sections from stressed mice treated with the formulation compared with stressed controls, alongside photographs of stomach interiors and evidence of WIRS-induced gastrointestinal bleeding. The authors note that these morphological observations were limited in the number of biological replicates and were not subjected to quantitative histopathological scoring or inferential statistical analysis. The quantitative weight of the evidence therefore rests on the macroscopic lesion assessments and the biochemical and molecular measurements, which together form a coherent picture of reduced injury, reduced inflammation, and enhanced antioxidant capacity in the treated animals.

The collaboration behind the work spans academia and industry. The research was supported by the Korea Ginseng Corporation under project number KGC-MD 20-221, which also supplied the study material, and three co-authors are employees of the KGC Research Institute, where their contributions were limited to HPLC and UPLC characterization of the study materials. The paper states that beyond this analytical role, the company had no influence on study design, animal experiments, formulation selection, data collection or analysis, interpretation, manuscript preparation, or the decision to publish. The animal experiments were approved by the Institutional Animal Care and Use Committee of Yeungnam University College of Medicine and conducted in compliance with ARRIVE guidelines, and the remaining authors declared no conflicts of interest.

For all its promise, the study is bounded by important limitations that the authors state plainly. The findings come from male mice subjected to a single acute stress paradigm, and they do not establish clinical efficacy, safety, an appropriate human intake level, or benefits for maintaining gastric health in people. The authors emphasize that evaluating the clinical applicability of the ginseng-ginger formulation will require validation of efficacy and safety in longer-term studies and in animal models of etiologically distinct forms of gastritis, followed by pharmacokinetic and bioavailability assessments and appropriately designed clinical trials. Until those steps are completed, the results should be read as preclinical evidence, not as a recommendation to self-treat with ginseng and ginger supplements.

Nevertheless, the study adds a meaningful data point to a growing body of research examining traditional food-based formulations through the lens of modern molecular pharmacology. By systematically screening formulation ratios, standardizing a seven-day dosing protocol, and interrogating inflammatory, oxidative, and acid-secretory pathways in parallel, the researchers have built a mechanistic scaffold that future studies can test and extend. If subsequent work confirms these protective pathways in other models and eventually in humans, the humble pairing of ginseng and ginger, long valued in traditional East Asian medicine, could find a scientifically grounded role in protecting the stomach against the damage that acute stress inflicts. For now, the message from Daegu is measured but intriguing: a 3:1 ginseng-ginger extract attenuated gastric hemorrhage, inflammation, and lipid peroxidation while boosting antioxidant defenses in stressed mice, and the full story of whether that protection can be bottled for people remains to be written.

Subject of Research: Gastroprotective effects of a ginseng-ginger extract formulation in a stress-induced gastritis mouse model

Article Title: Gastroprotective effects of a traditional ginseng–ginger formulation in a stress-induced gastritis mouse model

Article References: Jung, S.-R., Park, Y.-K., Cha, H.-N., Kwon, H. O., Kim, J. H., Bae, B. S., & Park, S.-Y. (2026). Gastroprotective effects of a traditional ginseng–ginger formulation in a stress-induced gastritis mouse model. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05612-y

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05612-y

Keywords: ginseng, ginger, stress-induced gastritis, gastroprotection, oxidative stress, inflammation, lipid peroxidation, glutathione peroxidase, mouse model, traditional medicine, preclinical study, gastric mucosa