A multi-herb formulation known as Wei-Mi-Shu Decoction alleviated gastric mucosal injury and reduced markers of systemic inflammation in rat models of chronic gastritis, according to an experimental investigation conducted by researchers at Qinghai University and Qinghai Provincial Hospital of Traditional Chinese Medicine. Chronic gastritis represents a widespread gastrointestinal condition defined by continuous mucosal inflammation and structural damage that often produces persistent indigestion, abdominal distension, and upper abdominal pain. In clinical practice, conventional Western pharmaceutical therapies frequently center around antibiotics and proton pump inhibitors, which can trigger adverse reactions and show notable rates of recurrence following treatment cessation. Within traditional Chinese medicine theory, a substantial subset of cases is classified under liver-stomach disharmony syndrome, a pathological pattern conceptualized as an imbalance in the liver-intestine-stomach axis where emotional distress and liver qi stagnation disrupt digestive mechanics and aggravate mucosal vulnerability.
To evaluate how traditional botanical strategies might address this pathological disorder, the investigative team established targeted animal models using thirty specific pathogen-free Sprague-Dawley male rats weighing approximately two hundred and thirty grams. Chronic gastritis was induced across designated cohorts by administering fifty-six percent ethanol at a dosage of eight grams per kilogram body weight by intragastric delivery every three days over a duration of four weeks. To simulate the dual pattern of liver-stomach disharmony combined with chronic gastritis, rats underwent ethanol modeling for three weeks followed by seven consecutive days of daily thirty-minute tail-clamping sessions designed to provoke aggressive agitation. Following model establishment, the animals were randomized into five distinct groups comprising healthy controls, model animals with chronic gastritis alone, model animals with liver-stomach disharmony chronic gastritis, and corresponding model groups treated with the herbal preparation, with each experimental group containing six animals.
The test intervention, Wei-Mi-Shu Decoction, was formulated as an empirical prescription developed by Chief Physician Junru Li containing eleven authenticated botanical and natural components totaling one hundred and sixty-five grams of raw crude drug per dose. The composition includes twenty grams of Bupleuri Radix, sixteen grams of Aurantii Fructus, ten grams of Angelicae Dahuricae Radix, sixteen grams of Bletillae Rhizoma, five grams of Notoginseng Radix et Rhizoma, six grams of Olibanum, six grams of Myrrha, thirty grams of Arcae Concha, thirty grams of Astragali Radix, ten grams of Arecae Semen, and sixteen grams of Herba Patriniae. The raw materials underwent standardized double aqueous decoction at the hospital preparation center, yielding an extract recovery of thirteen point eight percent and an approximate drug-extract ratio of seven point twenty-five to one. In the intervention cohorts, rats received the decoction by daily oral gavage at thirty-four point six grams per kilogram body weight, representing twice the clinical human equivalent dose calculated via body surface area conversion.
Systemic assessments revealed that both the standard gastritis model and the combined liver-stomach disharmony model produced marked behavioral changes, reduced food consumption, lethargy, dull fur, soft stools, and increased overall syndrome scores compared to healthy control rats. The animals subjected to tail clamping displayed significantly elevated syndrome scores relative to those experiencing ethanol alone, reflecting heightened emotional agitation and behavioral disturbance. Administration of Wei-Mi-Shu Decoction for four weeks reversed these composite impairment scores, restoring normal fecal consistency, coat luster, and food intake without producing observable adverse behaviors such as diarrhea, arched back posture, or piloerection. Furthermore, in five-minute open field behavioral tests, model animals exhibited sharp reductions in total ambulatory distance and average exploration speed, deficits that were significantly counteracted following four weeks of herbal gavage.
Histological examination of gastric mucosal tissues using hematoxylin and eosin staining demonstrated profound architectural damage in both untreated model groups, characterized by extensive cell shrinkage, glandular atrophy, necrosis, focal hemorrhages, residual cavitations, and marked inflammatory infiltration dominated by lymphocytes. Animals in the combined disharmony model exhibited more pronounced tissue destruction than animals with chemical gastritis alone. Treatment with the botanical decoction visibly preserved glandular organization and suppressed structural damage. Quantitative serum profiling by enzyme-linked immunosorbent assay confirmed that circulating concentrations of pro-inflammatory cytokines, specifically interleukin-1 beta, interleukin-6, interleukin-17, and tumor necrosis factor-alpha, were substantially elevated in model animals, with the disharmony group showing highest levels of interleukin-1 beta and tumor necrosis factor-alpha. Daily intervention with Wei-Mi-Shu Decoction produced statistically significant reductions across all four measured circulating inflammatory mediators.
The structural integrity of the protective gastric barrier was further assessed through specialized histochemical staining and transcript-level profiling. Staining with Alcian blue and periodic acid-Schiff reagent indicated an extensive depletion of protective mucosal mucins in model rats, which was significantly restored after herbal intervention. Concurrently, real-time quantitative polymerase chain reaction revealed severe down-regulation in the gastric expression of key tight junction and adhesion genes, including occludin, claudin, zonula occludens-1, and E-cadherin, alongside the antimicrobial factor intelectin-1. Daily treatment with Wei-Mi-Shu Decoction effectively promoted the relative messenger RNA abundance of each of these structural barrier components, demonstrating that the botanical formula aided in counteracting the molecular and physical degradation of the gastric epithelial barrier.
High-throughput profiling of colonic microbial contents using sixteen-S ribosomal RNA gene sequencing revealed clear differences in community organization across the animal cohorts. While alpha diversity metrics, including Chao1, Shannon, and Simpson indices, did not show statistically significant differences among the five cohorts, principal coordinate analysis based on Bray-Curtis distance showed distinct clustering. Permutational multivariate analysis of variance confirmed significant structural divergence among groups, accounting for over thirty-five percent of total community variation across dominant bacterial taxa such as Ligilactobacillus, Cryptobacteroides, Acutalibacter, Paramuribaculum, and members of the Muribaculaceae and Lachnospiraceae families. Parallel targeted metabolomics tracking bile acids in both colonic contents and serum demonstrated extensive shifts in primary and secondary bile acid pools, with notable variations in taurohyodeoxycholic acid, tauroursodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, and nor-deoxycholic acid.
Because bile acid signaling operates through specialized metabolic pathways, the researchers evaluated protein abundance of nuclear receptors in gastric tissue specimens. Both immunohistochemical analysis and Western blotting demonstrated that gastric levels of peroxisome proliferator-activated receptor alpha and retinoid X receptor were markedly decreased in untreated model animals, showing the most severe suppression in rats undergoing the combined disharmony protocol. Daily treatment with Wei-Mi-Shu Decoction significantly elevated the gastric protein concentrations of both receptors. In-silico target-directed network pharmacology analysis identified several candidate constituents within the prescription, such as flavonoids including quercetin and naringenin, as well as specific fatty acids and terpenoids, that were computationally predicted to bind these receptors, although these computational projections were based solely on documented database entries rather than direct chemical isolation.
To explore the regenerative capacity of the damaged stomach lining, the investigators tracked leucine-rich repeat-containing G-protein coupled receptor five positive stem cells, which maintain homeostatic epithelial renewal. Immunofluorescence staining demonstrated that the total count of these stem cells was severely diminished in both model groups, with the lowest counts detected in the combined disharmony model. Treatment with the herbal decoction significantly reversed this stem cell loss. Furthermore, transcript analyses showed marked declines in differentiated lineage markers within model gastric tissues, including surface mucous marker Muc5ac, parietal cell marker hydrogen-potassium ATPase, chief cell marker pepsinogen C, mucous neck marker Muc6, and endocrine marker somatostatin, all of which were significantly upregulated following decoction administration, reflecting improved differentiation across multiple functional gastric lineages.
Double immunofluorescence staining further revealed that the co-expression of peroxisome proliferator-activated receptor alpha, carnitine palmitoyl-transferase 1A, and very long-chain acyl-CoA dehydrogenase inside the gastric stem cell population was severely suppressed in disease models. Administration of the herbal formula significantly restored the abundance of stem cells co-expressing these metabolic enzymes, while whole-tissue quantitative PCR confirmed the parallel upregulation of fatty acid oxidation genes, including AOX-1, Cpt1a, Cpt1b, and ACADVL. The study authors emphasized several critical methodological limitations, noting that the experiments demonstrate phenotypic associations rather than direct molecular causality because gene silencing, receptor antagonist challenges, and dose-response experiments were not conducted. Additionally, the experimental cohort size of six rats per group was relatively modest, the administered extract dose exceeded conventional one gram per kilogram guideline thresholds, and chemical constituents were derived from public databases rather than direct chromatographic verification of the administered batch.
Subject of Research: Evaluation of Wei-Mi-Shu Decoction in rat models of chronic gastritis
Article Title: Wei-Mi-Shu Decoction ameliorates gastric mucosal injury in chronic gastritis with liver-stomach disharmony syndrome through the gut microbiota-hepatic bile acid metabolism axis
Article References: Zou, X., Jia, S., Wei, M., Qi, Y., Li, H., Liu, Y., & Li, J. (2026). Wei-Mi-Shu Decoction ameliorates gastric mucosal injury in chronic gastritis with liver-stomach disharmony syndrome through the gut microbiota-hepatic bile acid metabolism axis. Frontiers in Pharmacology, 17, Article 1983808. https://doi.org/10.3389/fphar.2026.1983808
Image Credits: AI Generated
DOI: 10.3389/fphar.2026.1983808
Keywords: chronic gastritis, traditional Chinese medicine, Wei-Mi-Shu Decoction, gastric mucosa, gut microbiota, bile acid metabolism, Lgr5 stem cells, pharmacology, Wei-Mi-Shu, Decoction, ameliorates, gastric
