Jul 2026· World Journal of Gastrointestinal Oncology· Vol 18· 0 citations· 33 references
TL;DR
YWXY alleviates gastric mucosal injury in combined SPEM and SSDS by regulating IL-1β and TNF-α, restoring the miR-7a-5p/Cdr1as axis, and suppressing WFDC2 expression, which indicates coordinated regulation of inflammatory cytokines, ncRNA networks, and metaplastic markers.
Abstract
Background
Gastric cancer develops through a sequence of atrophy, metaplasia, and dysplasia. Spasmolytic polypeptide-expressing metaplasia (SPEM) is a pivotal precancerous lesion associated with inflammation and noncoding RNA dysregulation. In traditional Chinese medicine (TCM), these pathological changes overlap with spleen-stomach deficiency syndrome (SSDS). Yiwei Xiaoyu granules (YWXY), a classical TCM formula, have demonstrated clinical benefit in chronic atrophic gastritis, yet their mechanistic actions in SPEM combined with SSDS remain unclear.
Aim
To investigate the protective effects and mechanisms of YWXY in a tamoxifen-induced SPEM and SSDS composite model.
Methods
A mouse model of tamoxifen-induced SPEM, with or without SSDS, was established. The effects of YWXY on gastric mucosa were evaluated by histological scoring, quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization (FISH). Key molecular endpoints included inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α], the miR-7a-5p/Cdr1as axis, and the metaplastic marker WFDC2. Statistical analysis was performed using two-way analysis of variance followed by Tukey’s multiple comparisons.
Results
YWXY exhibited time-dependent modulation of IL-1β, normalizing its expression at day 15 and suppressing persistent elevation at day 30. TNF-α overexpression in SPEM was significantly reduced by YWXY at both time points. Cdr1as downregulation in pathological groups was partially reversed by YWXY, while miR-7a-5p suppression in SSDS and SPEM + SSDS was restored toward baseline. WFDC2 induction in both SPEM and SSDS was significantly attenuated by YWXY, confirmed by qPCR and FISH. These findings indicate coordinated regulation of inflammatory cytokines, ncRNA networks, and metaplastic markers.
Conclusion
YWXY alleviates gastric mucosal injury in combined SPEM and SSDS by regulating IL-1β and TNF-α, restoring the miR-7a-5p/Cdr1as axis, and suppressing WFDC2 expression.
Findings suggest that PPP mitigates CAG and attenuates IM at least in part by suppressing the Pellino1/IRAK1/NF‐κB signaling pathway, indicating that it may serve as a promising therapeutic strategy for reducing inflammation‐associated gastric carcinogenesis.
Cheng Zhang, Fei Lu, Ting Ye et al.· Cell Biology International· 0 citations
Background Chronic atrophic gastritis (CAG) is a precancerous gastric lesion characterized by persistent inflammatory injury, glandular atrophy, and impairment of gastric mucosal barrier-associated integrity. Huangjin Shuangshen Decoction (HJSS) has shown therapeutic potential in gastritis-related disorders, but its effects on CAG and the underlying mechanism remain unclear. This study investigated whether HJSS alleviates CAG by modulating inflammation-associated barrier dysfunction. Methods CAG was induced in mice by MNNG combined with ranitidine and irregular feeding, followed by treatment with different doses of HJSS, with folic acid as a positive control. Histopathology, gastric function indices, inflammatory mediators, apoptosis-related markers, and barrier-associated molecules were assessed in vivo. MNNG-injured GES-1 cells treated with HJSS-medicated serum were used for in vitro validation. Transcriptomic analysis, network pharmacology, and pharmacological inhibition were integrated to explore the underlying mechanisms. Results HJSS alleviated gastric mucosal atrophy and histopathological injury, improved gastric functional impairment, reduced inflammatory burden, and attenuated apoptosis-associated epithelial injury in experimental CAG. HJSS also promoted the recovery of gastric mucosal barrier-associated molecules, including CFTR, ZO-1, MUC5AC, Occludin, and Claudin-1. Integrated transcriptomic and network pharmacology analyses highlighted an inflammation–barrier framework involving TNF-related signaling and CFTR-associated regulation. In vitro, HJSS mitigated MNNG-induced epithelial injury, whereas CFTR inhibition attenuated the HJSS-associated restoration of CFTR and ZO-1. HJSS was further associated with suppression of TNF/NF-κB signaling and reduced p65 nuclear translocation. Conclusion HJSS alleviates MNNG-induced CAG by attenuating inflammatory injury and promoting the recovery of gastric mucosal barrier-associated molecular features. Its protective effects are associated with suppression of TNF/NF-κB signaling and involvement of CFTR-associated regulation, supporting an inflammation–barrier mechanism underlying the action of HJSS in CAG.
Shuo Zhang, Shuya Zhang, Mengyi Wang et al.· Frontiers in Immunology· 0 citations
Gastric intestinal metaplasia (GIM) is a typical precancerous lesion of gastric cancer (PLGC). Previous studies have demonstrated that Xinkai Kujiang formula can effectively alleviate GIM, but its underlying mechanism remains largely unclear.
The GIM rat model was established using 2% sodium salicylate and 20 mmol/L sodium deoxycholate, and then the rats were treated with Banxia Xiexin Decoction (BXD) and Xinkai Kujiang Decoction (XKD) for 4 weeks. Multi-omics analyses including 16 S ribosomal RNA gene sequencing, transcriptomics, single-cell RNA sequencing, network pharmacology, and component identification were performed to explore the therapeutic mechanisms of Xinkai Kujiang formula on GIM.
In the model rats, severe gastric mucosal atrophy was observed, characterized by disordered glands and goblet cells. Following intervention with BXD and XKD, gastric mucosal thickness was restored, glandular structures became regularly arranged, and the number of metaplastic goblet cells markedly decreased. Microbiota profiling of gastric mucosa revealed significant enrichment of
Lactobacillus
and
Enterococcus
in the model group. These abundances were reduced in the BXD group, and short-chain fatty acid-producing bacteria such as
Alistipes
and
Lachnospira
were enriched. In the intestine, opportunistic pathogens like
Streptococcus
and
Enterococcus
were enriched in the model group, whereas
Corynebacterium
and
Bifidobacterium
were enriched in the XKD group. Transcriptomic analysis presented that BXD upregulated innate immune-related genes in the gastric mucosa, and single-cell RNA sequencing (scRNA-Seq) showed that XKD alleviated GIM by inhibiting the VEGF and HIF-1α pathways, reducing angiogenesis, suppressing inflammatory infiltration, and regulating energy metabolism.
BXD and XKD improve gastrointestinal microbiota disorders and metabolic disorders, enhance gastric mucosal immunity, and inhibit the VEGF and HIF-1α pathway. Collectively, these multi-omics data provide novel insights into the therapeutic mechanisms of Xinkai Kujiang formula for GIM.
Jiao Xiang, Yu-Qin Cheng, Zhaolin Wang et al.· Frontiers in Pharmacology· 0 citations
Evaluating the preventive and therapeutic effects of RQMJ on CAG and its intervention in the inflammation–cancer transition process highlights the potential pharmacological value and therapeutic prospects of RQMJ in inflammation-driven gastric diseases.
Fengyu Huang, Peiping Chen, Daiyue Ding et al.· Chinese Medicine· 0 citations
Chronic atrophic gastritis (CAG) is a well-recognized precursor of gastric cancer (GC). Spasmolytic polypeptide-expressing metaplasia (SPEM) is a key intermediate state during this process, representing a reparative response to gastric mucosal injury, and may promote the development of malignancy under persistent inflammation. Recent studies have suggested that SPEM is not a static lesion but a dynamic and heterogeneous process regulated by epithelial injury, oxyntic atrophy, and chronic inflammation. This review summarizes current knowledge on cellular plasticity, lineage dynamics, and molecular mechanisms underlying SPEM formation and progression in CAG. We focus on recent advances in oxyntic atrophy, immune cell and inflammation, as well as oxidative stress in gastric epithelial remodeling, and highlight emerging evidence implicating ferroptosis, a regulated form of iron-dependent lipid peroxidation, in gastric mucosal inflammation and SPEM development. By integrating classical models of GC with recent mechanistic insights, we aim to discuss the role of SPEM in CAG-associated GC risk and to identify potential therapeutic targets related to oxyntic atrophy, inflammation, and ferroptosis. These emerging findings offer new perspectives for future research aiming at risk stratification and precision prevention.
Xin Quan, Linglong Ji, Tian He et al.· Journal of Digestive Disease...· 0 citations
It is demonstrated that HEP exerts gastroprotective effects against CAG through coordinated anti-inflammatory, antioxidant, and structure-dependent NF-κB inhibitory actions, supporting its potential as a promising natural agent for CAG intervention.
Ping Li, Jianran Hu, Yan-juan Yang et al.· International Journal of Bio...· 0 citations