Elucidating the Activity of E-Lian Granule in Alleviating Chronic Atrophic Gastritis: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.
Jul 2026· Current Computer - Aided Drug Design· Vol 22· 0 citations
Medicine
TL;DR
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.
Abstract
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.
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.
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Aim Given the limited availability of safe and effective treatments for inflammatory bowel disease (IBD), we applied an integrated network pharmacology approach to systematically map the targets and pathways of cordycepin, a bioactive compound from Cordyceps militaris, in experimental colitis. Methods Cordycepin was administered intraperitoneally during dextran sulfate sodium (DSS) exposure in mice, with efficacy evaluated by the disease activity index (DAI) and histopathological analysis. Network pharmacology analysis (TCMSP, CTD, SEA, BATMAN-TCM, GeneCards, and PharmMapper), molecular docking, and molecular dynamics (MD) simulations were performed to identify and validate potential core targets. AKT1 and tight junction protein ZO-1 expression in colonic tissues was assessed by immunohistochemistry (IHC). The involvement of AKT signaling in cordycepin’s effects on tight junction integrity and mitochondrial function was further investigated in lipopolysaccharide (LPS)-treated Caco-2 cells using the AKT inhibitor MK2206. Results Cordycepin (50 mg/kg) significantly attenuated body weight loss and DAI elevation in DSS-treated mice. A total of 361 putative cordycepin-related targets were identified from six public databases, while 2, 072 UC-related targets were obtained from GeneCards, OMIM, and DisGeNET. A total of 199 overlapping targets were functionally enriched in processes including “TNF signaling pathway”, “PI3K-AKT signaling pathway” and “cellular response to lipopolysaccharide”. The PPI network identified 8 core targets, among which AKT1, NFKB1, RELA and TP53 demonstrated strong binding affinity (binding free energy<-6.0 kcal/mol) with cordycepin in molecular docking and were enriched within the PI3K/AKT pathway. IHC analysis showed that cordycepin reversed alterations of colonic AKT1 and ZO-1 levels in DSS mice. In Caco-2 cells, AKT inhibition with MK2206 attenuated the protective effects on tight junction integrity and mitochondrial function against LPS-induced injury. Conclusion These findings suggest that prophylactic administration of cordycepin, a promising natural compound, alleviates experimental colitis, potentially through modulation of the PI3K/AKT1 signaling pathway and restoration of epithelial barrier integrity.
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XieRiGa-4 (XRG-4) is a widely used formulation in Mongolian medicine for
the treatment of kidney dysfunction, yet its active constituents and underlying mechanisms of action
remain poorly characterized. This study aims to identify active constituents, key targets, and potential
pharmacological mechanisms of XRG-4 in protecting against kidney injury using network pharmacology,
molecular docking, and in vivo and in vitro validation.
A rat kidney injury model was established by pylorus ligation to evaluate XRG-4 efficacy.
Active components of XRG-4 were characterized by liquid chromatography-mass spectrometry (LCMS),
and candidate targets were obtained from public databases. Network pharmacology analyses, including
protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and
Genomes (KEGG) analyses, were conducted to identify core bioactive components, potential targets,
and signaling pathways. Molecular docking assessed binding affinities between active compounds and
core targets, and Western blot analysis validated expression of key targets.
Biochemical analysis revealed that serum creatinine (CRE) and urea (URE) levels were significantly
higher in the model group than in the normal group (P < 0.01) and were significantly reduced after
XRG-4 treatment (P < 0.01), indicating a renal protective effect. Cell viability was markedly decreased in
the model group (P < 0.01) and significantly improved in XRG-4-treated groups (P < 0.01). A total of 20
bioactive compounds, including the top 10 cationic and anionic constituents, and 253 overlapping targets
associated with XRG-4 and kidney injury were identified. Network analysis indicated a central role of the
EGFR signaling pathway in XRG-4 efficacy. Molecular docking revealed that five key compounds, 6-
Hydroxypurine, Hymecromone, Gardenoside, Geniposide, and Phenprobamate, displayed strong binding
affinities with three core targets, Slc22a5, Mrps9, and EGFR. Western blot analysis further confirmed
that Slc22a5 (P < 0.05) and Mrps9 (P < 0.01) expression was significantly reduced in the model group
and markedly upregulated following XRG-4 treatment.
This study confirms that Mongolian medicine XRG-4 improves renal function and alleviates
kidney injury. Using network pharmacology, molecular docking, and experimental validation, its
main active components were found to bind to core targets including EGFR, Slc22a5, and Mrps9, regulate
the EGFR signaling pathway, and upregulate Slc22a5 and Mrps9 expression, thereby exerting a
nephroprotective effect and providing a scientific basis for its clinical application.
This study clarifies the nephroprotective effects of XRG-4 and demonstrates its capacity
to attenuate kidney injury through the EGFR signaling pathway. These findings provide a scientific
rationale for clinical use of XRG-4 in kidney diseases and support further development of XRG-4 as a
potential nephroprotective agent in Mongolian medicine.
Zhi-Chao Qi, Qing Bai, Ling Ling et al.· The Natural Products Journal· 0 citations
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.