Mechanisms of Hericium erinaceus polysaccharides on chronic atrophic gastritis: An integrated study of network pharmacology, molecular docking, in vivo experiments, and scRNA-seq.

Elucidating the Activity of E-Lian Granule in Alleviating Chronic Atrophic Gastritis: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.

INTRODUCTION Chronic Atrophic Gastritis (CAG) and Intestinal Metaplasia (IM) are critical precancerous lesions of gastric cancer. E-Lian granule (ELKL), a traditional Chinese medicine formula, has demonstrated favorable clinical efficacy in treating precancerous gastric lesions; however, its underlying molecular mechanisms remain unclear. METHODS A comprehensive approach integrating network pharmacology, molecular docking, and experimental validation was employed to investigate the pharmacological mechanisms of ELKL against CAG and IM. Potential active compounds, therapeutic targets, and signaling pathways were identified through database analysis, Protein-Protein Interaction (PPI) networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was utilized to evaluate compound-target interactions. In vitro experiments were performed using MNNG-induced human Gastric Epithelial Cells (GES-1) treated with magnoflorine, columbamine, or 3-O-acetyl-glycyrrhetinic acid, and in vivo validation was conducted in a CAG mouse model. RESULTS A total of 178 overlapping therapeutic targets were identified. KEGG analysis revealed that the TNF, MAPK, and PI3K/Akt signaling pathways were closely associated with the therapeutic effects of ELKL. AKT1, MAPK1, and NFKB1 were identified as key hub targets. Molecular docking demonstrated strong and stable binding affinities of magnoflorine, columbamine, and 3-O-acetyl-glycyrrhetinic acid toward these targets. In vitro and in vivo assays comprehensively confirmed that these compounds significantly attenuated inflammatory cytokine secretion and inhibited the expression of AKT1, MAPK1, and NFKB1. DISCUSSION These findings indicate that ELKL exerts significant anti-inflammatory effects through the multi-component and multi-target regulation of inflammatory signaling pathways, thereby supporting its therapeutic potential in preventing the progression of CAG and IM. CONCLUSION The representative active compounds identified from ELKL may ameliorate CAG and IM by regulating the TNF, MAPK, and PI3K/Akt signaling pathways.

Piwei Peiyuan Pill Ameliorates Chronic Atrophic Gastritis and Intestinal Metaplasia at Least in Part by Inhibiting the Pellino1/IRAK1/NF‐κB Signaling Axis

Chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) is a key precancerous lesion that may progress to intestinal‐type gastric adenocarcinoma. Piwei Peiyuan Pill (PPP) has shown significant clinical efficacy in ameliorating CAG with IM, but its active components and underlying mechanisms remain unclear. High‐performance liquid chromatography (HPLC) and ultra‐high performance liquid chromatography coupled with high‐resolution mass spectrometry (UHPLC‐HRMS) were used to identify the components of PPP and the active ingredients in PPP‐containing serum. The therapeutic efficacy and potential mechanisms of PPP were further investigated via transcriptomic sequencing and experimental validation. UHPLC‐HRMS analysis of PPP‐containing serum identified several bioactive components, including esculin, lithospermic acid, and atractylenolide III. In CAG rats, PPP significantly ameliorated gastric mucosal damage and reduced serum IL‐6 and TNF‐α levels. Transcriptomic results showed that IRAK1 was highly expressed in CAG patients with IM and associated with activation of the NF‐κB pathway. PPP intervention dose‐dependently suppressed hyperactivation of the Pellino1/IRAK1/NF‐κB axis and decreased the expression of intestinal metaplasia markers CDX1 and MUC2. Additionally, PPP improved immune function by increasing the proportion of CD4+ T cells and decreasing the proportion of CD8+ T cells in CAG model rats. Taken together, these 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.

Renqing Mangjue modulates chronic atrophic gastritis inflammation-cancer transition via the cGMP–PKG/PI3K–AKT pathway

Chronic atrophic gastritis (CAG) is a critical stage in the progression from inflammation to cancer and is closely associated with an increased risk of gastric cancer (GC). Renqing Mangjue (RQMJ), a traditional Tibetan herbal remedy, has shown diverse pharmacological properties, including regulation of gastrointestinal function and anti-inflammatory effects. However, the specific effects and mechanisms by which RQMJ influences the transition from inflammation to cancer remain unclear. This study aimed to evaluate the preventive and therapeutic effects of RQMJ on CAG and its intervention in the inflammation–cancer transition process, with a focus on exploring the underlying molecular mechanisms. RQMJ was chemically characterized by UPLC-Q-TOF–MS/MS and HPLC. A rat model of CAG and its inflammation-cancer transition was established and treated with different doses of RQMJ. The therapeutic effects of RQMJ were evaluated by gross gastric mucosal observation, ELISA, histopathological staining, immunohistochemistry, and Western blot analysis. In vitro, the effects of RQMJ on inflammation and migration of the gastric precancerous cell model (MC cells) were assessed using ELISA, wound-healing, Transwell migration, and Western blot assays. RNA sequencing and molecular biology techniques were then employed to explore the underlying mechanisms, and key targets were further validated in both in vivo and in vitro experiments. Finally, C-type natriuretic peptide (CNP) was used to verify the involvement of the identified signaling pathway. A total of 2780 chemical constituents were identified in RQMJ. A dynamic rat model of CAG and its progression to GC was established. During CAG, persistent inflammation and aberrant PI3K–AKT activation formed a positive-feedback loop, driving FAK overexpression and epithelial–mesenchymal transition (EMT)-related changes, which remained active in GC despite partial reduction of inflammation. RQMJ markedly alleviated gastric mucosal injury, suppressed intestinal metaplasia, and improved gastrointestinal function. It also reduced pro-inflammatory mediators (TNF-α, IL-1β, CRP), increased IL-10, and downregulated tumor-related markers (Ki-67, Vimentin, CA19-9). In vitro, RQMJ inhibited MC cell proliferation and migration, suppressed inflammatory and EMT-related proteins. Mechanistically, RQMJ activated the cGMP–PKG pathway and inhibited the PI3K–AKT signaling pathway, thereby disrupting inflammatory amplification. This further downregulated extracellular matrix (ECM)–receptor interaction molecules (TGF-β, FAK, Itga2), ultimately blocking the inflammation–cancer transition. RQMJ may activate the cGMP–PKG signaling pathway while suppressing aberrant PI3K–AKT activation, thereby reducing inflammatory cytokine levels and inhibiting ECM remodeling and the EMT-associated process, and thus indirectly interrupting the inflammation-cancer cascade. These findings highlight the potential pharmacological value and therapeutic prospects of RQMJ in inflammation-driven gastric diseases.

Elucidating the molecular mechanisms of paeoniflorin intervention in oral lichen planus: a computational biology and bioinformatics–based research strategy

Background Oral lichen planus (OLP) is a chronic inflammatory mucosal disease with a risk of malignant transformation and limited long-term therapeutic options. Paeoniflorin (PF), a natural monoterpene glycoside, exhibits multi-target anti-inflammatory and immunomodulatory properties, but its systematic mechanisms against OLP remain elusive. Methods We employed an integrative framework combining network pharmacology, transcriptomic cross-validation, molecular docking, and molecular dynamics (MD) simulations. Public databases were mined to identify PF targets and OLP-related genes. Core targets were prioritized via protein-protein interaction (PPI) network topology and further validated using OLP tissue transcriptomic datasets (GSE52130 and GSE213349). Functional enrichment analyses were performed, followed by structural validation of PF–target binding via molecular docking and 100-ns MD simulations. Results Sixty-eight overlapping targets between PF and OLP were identified. PPI network analysis and transcriptomic cross-validation pinpointed eight core targets: AKT1, IL6, MMP9, STAT3, TNF, IL1B, PTGS2, and PDE4B. Mechanistically, these targets converged on the TNF, PI3K–Akt, and MAPK signaling pathways, regulating inflammatory response, cell migration, apoptosis, and protease activity at membrane microdomain and extracellular matrix interfaces. Molecular docking showed PF binding affinities comparable to or exceeding reference inhibitors (e.g., STAT3: −9.27 vs. Stattic −9.16 kcal/mol). MD simulations confirmed stable conformational binding, with the STAT3 and PDE4B complexes exhibiting the most balanced rigidity and lowest ligand RMSD (0.09–0.10 nm). Conclusion This study provides a systems-level map of PF’s multi-target intervention in OLP, highlighting a composite anti-inflammatory–immune reprogramming–pro-repair axis centered on core inflammatory kinases and proteases. The structural validation of key targets establishes a mechanistic rationale for PF as a promising therapeutic candidate, warranting further preclinical and clinical development for OLP management.

Exploring the anti-Helicobacter pylori activity of Guluchyadi Kashayam through in-vitro and in-silico analysis

Huangjin Shuangshen decoction alleviates chronic atrophic gastritis by suppressing TNF/NF-κB signaling and promoting CFTR-associated gastric mucosal barrier repair

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.