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