Research Paper Volume 15, Issue 23 pp 13998—14018
Modified Chaishao Liujunzi Decoction inhibits bile acid-induced gastric intestinal metaplasia: from network prediction to experimental verification
- 1 Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China
- 2 Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
Received: February 27, 2023 Accepted: November 2, 2023 Published: December 10, 2023
https://doi.org/10.18632/aging.205285How to Cite
Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Modified Chaishao Liujunzi Decoction (MCLD) is a traditional Chinese medicine formula that is used mainly to improve clinical symptoms, alleviate gastric mucosal inflammation, and improve gastric mucosal lesions in patients with gastric intestinal metaplasia (GIM). GIM is considered a precancerous gastric cancer (GC) lesion (PLGC) and exploring effective intervention measures for GIM is of great importance for the prevention of GC. The purpose of this study was to reveal the potential molecular mechanism of MCLD in improving GIM induced by bile acid (BA) using network pharmacology and experimental validation. Through network pharmacology, we speculated that MCLD could act on GIM by driving the epidermal growth factor receptor (EGFR)/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. After that, we used deoxycholic acid (DCA) to treat GES-1 cells to simulate BA-induced GIM and observed the effects of MCLD treatment. The results indicate that MCLD can significantly inhibit DCA-induced cell proliferation and down-regulate the expression of pro-inflammatory cytokines and intestinal-specific markers. At the same time, MCLD also negatively regulated the expression of genes and proteins of the EGFR/PI3K/AKT/mTOR pathway. Combination with EGFR agonists and inhibitors suggested that MCLD may improve GIM by inhibiting the EGFR/PI3K/AKT/mTOR pathway, which may be related to its inhibition of DCA-induced cell proliferation through this pathway. In conclusion, MCLD may improve BA-induced GIM through the EGFR/PI3K/AKT/mTOR pathway, as predicted by network pharmacology, and is a potential Chinese medicine prescription for the treatment or reversal of GIM.
Abbreviations
GIM: Gastric intestinal metaplasia; MCLD: Modified Chaishao Liujunzi Decoction; GC: Gastric cancer; TCM: Traditional Chinese medicine; BA: Bile acid; DCA: Deoxycholic acid; CDX2: Caudal-related homeobox 2; MUC2: Mucin 2; CAG: Chronic atrophic gastritis; Hp: Helicobacter pylori; PPI: protein-protein interaction; GO: Enrichment of Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; OB: Oral Bioavailability; DL: Drug-Like; TCMSP: Traditional Chinese Medicine Systems Pharmacology; MTT: 3-(4;5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AKT1: RAC-alpha serine/threonine-protein kinase; IL-6: interleukin-6; TNF-α: Tumor necrosis factor α; IL1β: Interleukin-1 beta; PI3K: Phosphoinositide 3-kinase; EGFR: Epidermal growth factor receptor; mTOR: mammalian target of rapamycin; VEGFA: vascular endothelial growth factor A; STAT3: Signal transducer and activator of transcription 3; BP: biological process; DC: Degree Centrality; BC: Betweenness Centrality; CC: Closeness centrality.