A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Mechanisms of Si-Wu Decoction in the treatment of ulcerative colitis revealed by network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Wu Decoction (SWD) is a traditional Chinese medicine decoction. SWD is commonly used to treat blood deficiency syndrome. It is also used to treat some ulcerative colitis (UC) patients now, but the mechanism of action remains unclear. AIM OF THE STUDY: This study explored the efficacy and mechanism of action of SWD in treating UC based on network pharmacology and related experimental validation. MATERIALS AND METHODS: Several databases were used to screen SWD for major active ingredients, targets of the ingredients, and UC disease genes. Cytoscape 3.8.2 software was used for topological analysis to construct the drug-compound-disease gene-target relationship network. The String database platform was used to construct the target protein interaction network. The DAVID (Database for Annotation, Visualization and Integrated Discovery) database was used to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for the key targets. DSS (Dextran Sulfate Sodium)-induced UC mouse model was used to evaluate the in-vivo activity of SWD. Western Blot analysis and quantitative polymerase chain reaction were performed to verify the targets in the related pathways. RESULTS: Network pharmacology revealed that the SWD targeted pathway network involved 12 core targets and 15 major pathways. SWD may play a part by targeting key targets such as nuclear factor-kappaB (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) pathway, and several mitogenic pathways. We showed that SWD largely restored the colorectal structure in UC model mice. Compared to the model group, the SWD group showed reduced infiltration of inflammatory cells. SWD significantly decreased the mRNA levels of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-alpha), IL-1b (Interleukin-1beta) and other pro-inflammatory factors. Western Blot results showed that SWD concentration-dependently inhibited STAT3 and NF-κB activation in DSS-treated colon tissue. CONCLUSION: Our findings suggest that SWD treats UC by inhibiting STAT3 and NF-κB signaling pathways, reducing the expression of inflammatory cytokines, and improving epithelial repair in experimental colitis, thus shedding light on the mechanisms by which SWD exerts its effects on UC.