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

The research team, led by investigators at Chonnam National University in collaboration with Nong Shim Co. Ltd. and Dongshin University, began with a large-scale screening effort. Thirty-seven lactic acid bacteria strains maintained in their laboratory were tested for the two traits that any probiotic hoping to survive the journey to the stomach must possess: tolerance to strongly acidic conditions and resistance to bile. The bacteria were incubated in buffers adjusted to pH 2.0, 2.5, and 3.0, and separately in growth medium containing 0.5 percent Oxgall, a purified bovine bile preparation. Viable cell counts, expressed as log colony-forming units per milliliter, revealed dramatic differences. At pH 2.0, one strain retained nearly 4.89 log CFU/mL while two common dairy strains, Lacticaseibacillus casei and Limosilactobacillus reuteri, were wiped out entirely. From this gauntlet, seven strains emerged, and three were advanced for full evaluation: Lacticaseibacillus rhamnosus NS2301G1, Limosilactobacillus fermentum NS2301G2, and Levilactobacillus brevis NS2301G3, all originally isolated from kimchi.

Safety testing preceded any therapeutic claims. The three strains were profiled for antibiotic susceptibility using Etest strips against nine clinically relevant antibiotics, including ampicillin, vancomycin, gentamicin, erythromycin, and tetracycline, with minimum inhibitory concentrations interpreted against the microbiological cut-off values published in current European Food Safety Authority guidance. All measured values fell at or below the applicable thresholds. Hemolytic activity, a key virulence concern for any bacterium proposed for consumption, was assessed on blood agar plates, and all three strains displayed gamma-hemolysis, meaning no red blood cell destruction whatsoever. These results position the strains as credible candidates for incorporation into functional foods rather than merely as laboratory curiosities.

Before moving into animals, the team tested the bacteria against human gastric epithelial cells. NCI-N87 cells, a widely used human stomach cancer-derived epithelial line, were pretreated for six hours with each live bacterial suspension at one million colony-forming units per milliliter and then assaulted with a solution of 5 percent ethanol in 10 millimolar hydrochloric acid. The corrosive treatment alone drove cell viability down to roughly 60 percent of untreated controls. Pretreatment with the bacteria pulled viability back to between 89 and 102 percent, with NS2301G2 and NS2301G3 effectively restoring survival to control levels and exceeding the protection offered by omeprazole, which reached 88 percent. The protection was accompanied by molecular changes: the chemical assault slashed expression of MUC5AC, the gene encoding the gel-forming mucin that forms the stomach’s viscoelastic protective lining, by nearly 70 percent, along with DEFB4B, an inducible beta-defensin involved in antimicrobial defense, and PTGER3, a prostaglandin receptor gene tied to mucosal protection. Bacterial pretreatment significantly blunted or reversed all three losses.

The decisive experiment took place in living animals. Thirty male Sprague-Dawley rats were divided into six groups and received daily oral doses for fourteen days: phosphate-buffered saline for the control and injury groups, omeprazole at 20 milligrams per kilogram, or one of the three bacterial strains at one billion colony-forming units per animal per day. On the final day, after a 24-hour fast, all animals except the controls received two milliliters of 60 percent ethanol containing 150 millimolar hydrochloric acid by oral gavage. One hour later, the stomachs were harvested and the hemorrhagic lesion area quantified using image analysis software. The untreated injury group developed lesions covering 24.2 square millimeters, or about 21.4 percent of the total gastric surface. Pretreatment shrank that damage dramatically: omeprazole reduced lesions to 7.8 square millimeters, NS2301G1 to 10.5, NS2301G2 to 13.1, and NS2301G3 to just 6.2 square millimeters, meaning the L. brevis strain protected the stomach better than the blockbuster acid-suppressing drug itself.

Histological examination under the microscope confirmed what the naked eye suggested. Stomach sections from the injury group showed devastated glandular architecture, epithelial cell necrosis, mucosal erosion, focal hemorrhage, and dense inflammatory infiltration. In contrast, tissues from bacteria-treated rats retained comparatively preserved glandular structures with far less necrosis and bleeding, findings evaluated by a pathologist blinded to group allocation. Western blot analysis of the tissue proteins added a mechanistic layer: the injury group showed markedly elevated interleukin-6, a pro-inflammatory cytokine, alongside sharply depressed MUC5AC protein, the workhorse mucin of the gastric mucus barrier. Bacterial pretreatment suppressed IL-6 and preserved MUC5AC, indicating that the bacteria were not merely diluting the insult but actively reprogramming the stomach’s inflammatory and barrier-maintenance machinery.

Quantitative PCR on gastric tissue deepened the molecular picture. Ethanol and hydrochloric acid exposure cut Muc5ac messenger RNA nearly in half and reduced the anti-inflammatory cytokine gene Il10 by about 54 percent, while driving pro-inflammatory mediators into overdrive: Ptgs2, the gene encoding cyclooxygenase-2, rose almost 89 percent, Il6 surged nearly fivefold, and Tnf nearly doubled. The bacterial treatments partially reversed every one of these shifts. NS2301G1 proved the strongest all-around performer, restoring Muc5ac to 0.82 normalized units and pushing Il10 to 1.38 while suppressing Il6 more effectively than its counterparts. Serum cytokine measurements told a parallel story of systemic protection: injury rats showed TNF-alpha climbing from about 16 to 118 picograms per milliliter, yet NS2301G1-treated animals capped the surge at roughly 41 picograms per milliliter, with IL-6 showing a similar attenuation across all three bacterial groups.

Why did closely related bacteria perform so differently? The authors turned to previously published genome sequences of the three strains for clues. All three share a core toolkit of glutathione- and thioredoxin-associated redox defense genes, including gshAB, trxA, trxB, and tpx, suggesting a common capacity to withstand oxidative stress, a central driver of ethanol-induced mucosal damage. But the strain-specific extras are telling. NS2301G1 uniquely carries bsaA, encoding glutathione peroxidase, and npr, encoding NADH peroxidase, an apparent added capacity for peroxide detoxification that may underpin its strong anti-inflammatory performance. NS2301G3 stands apart with katA, a catalase gene, and a complete glutamate decarboxylase system, gadB and gadC, which consumes intracellular protons to convert glutamate into gamma-aminobutyric acid, conferring exceptional acid resistance, a plausible explanation for its unmatched reduction of macroscopic lesions under the brutal acid challenge. The researchers are careful to note that genomic annotation alone does not prove expression or causation, and they frame these candidates as hypotheses demanding transcriptomic and metabolomic follow-up.

The broader implications reach from the clinic to the dairy aisle. Proton pump inhibitors, while effective, have drawn mounting scrutiny over associations with acute and chronic kidney disease and concerns about long-term use, and resistance complicating Helicobacter pylori eradication continues to erode conventional options. Lactic acid bacteria offer an appealing alternative strategy: rather than suppressing acid, they reinforce the mucosal mucus barrier, temper inflammatory signaling, and bolster antioxidant defenses, all through organisms with an established safety record in fermented foods. Because these particular strains are acid- and bile-tolerant kimchi isolates, they are natural candidates for fermented dairy products and other animal-derived food matrices, where they could deliver gastroprotective benefits alongside nutrition. The study’s authors emphasize that their findings, while striking, come from an acute animal model, and that human trials, technological characterization as starter cultures, and identification of the precise bacterial components responsible remain the essential next steps before a kimchi-derived probiotic could become a mainstream prescription for stomach health.

Subject of Research: Comparative gastroprotective effects of lactic acid bacteria strains against ethanol/HCl-induced gastric injury

Article Title: Comparative evaluation of the gastroprotective effects of lactic acid bacteria strains against ethanol/HCl-induced gastric injury

Article References: Kim, K., Pyeon, M., Shin, S., Lee, J., Jeon, S., Son, B., Kim, J. H., Lee, G., Lee, J. H., & Oh, S. (2026). Comparative evaluation of the gastroprotective effects of lactic acid bacteria strains against ethanol/HCl-induced gastric injury. Food Science of Animal Resources, 46(1), Article 103. https://doi.org/10.1007/s44463-026-00109-1

Image Credits: AI Generated

DOI: 10.1007/s44463-026-00109-1

Keywords: lactic acid bacteria, probiotics, gastric injury, kimchi, gastric mucosa, ethanol-induced ulcer, omeprazole, MUC5AC, inflammation, Lactobacillus, functional foods, gastroprotection