Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanisms of Huazhuojiedu Decoction to Treat Chronic Atrophic Gastritis

Abstract

Background. Chronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa’s transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment. Purpose. This study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation. Methods. The active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The “herb-compound-target-disease” and the “herb-target-pathway” network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa’s histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction. Results. A total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups. Conclusion. Taken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.

16S rRNA sequencing-based evaluation of the protective effects of Hua-Zhuo-Jie-Du on rats with chronic atrophic gastritis

“…GC comprises the following precancerous steps: chronic active gastritis → chronic atrophic gastritis → gastric intestinal metaplasia → gastric epithelial dysplasia [ 18 ]. Inflammation, cell proliferation and apoptosis, autophagy dysfunction, energy metabolism disorders, and other factors may contribute to the development process, although the exact pathogenesis is still unclear [ 14 , 17 , 19 , 20 ]. The common therapies used for CAG focus on symptomatic treatment and are often not completely effective.…”

“…The use of HZJD is based on turbid toxic syndrome. It functions to clear away heat, and detoxify and invigorate the spleen to remove dampness and has achieved good results in the treatment of CAG [ 14 , 19 ]. However, the regulating effect of HZJD on the intestinal flora is still unclear.…”

“…Makino (Jiaogulan). In previous research, through network pharmacology and experimental verification, the important components and possible targets of HZJD in the treatment of CAG were obtained [ 14 ]. Previous clinical experiments have also confirmed that HZJD had positive clinical effects [ 15 ].…”

Determination of the protective effects of Hua‐Zhuo‐Jie‐Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing

“…Makino (Jiaogulan). Previous studies have reported on the possible mechanism of HZJD in the treatment of CAG, which is mainly suggested to be due to the regulation of cell proliferation and apoptosis [ 13 , 14 ]. In a clinical study, we compared the clinical efficacy, gastroscopic efficacy and pathological efficacy of HZJD and ALaTanWuWeiWan for gastric precancerous lesions, and found that the efficacy of HZJD was better than the control group ( P < 0.05), the mechanism was thought to be associated with the decreased expression of HIF-1α, and VEGF and the increased expression of PTEN [ 15 ].…”

“…TCM is a coordinated system for the treatment of multitarget and multicomponent diseases. In a network pharmacology study, we constructed the “herb-compound-target-disease” network diagrams, and found that 156 active ingredients in HZJD had common targets with CAG [ 13 ]. Metabolomics is a systems biology approach that comprehensively describes the pharmacological action of drugs and the association between disease processes and specific biological pathways.…”