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Exploration of the mechanism of the Mongolian medicine Tonglaga-5 (通拉嘎-5) for the treatment of n-methyl-n′-nitro-n-nitrosoguanidine-induced chronic atrophic gastritis based on network pharmacology and metabolomics
Received date: 2024-12-14
Accepted date: 2025-03-25
Online published: 2025-05-08
Supported by
New Quality Control Model of Mongolian Medicine Tonglaga-5 “Qingzhuo Shenghua” Based on “Stomach Blood Bone Correlation Tracking”(82160745);Grassland Talent Rolling Support Program([2023]3);Research on the Mechanism of Mongolian Prescription Tonglaga-5 in Treating Chronic Atrophic Gastritis based on Multiomics Integration(YKD2024ZD001);Preparation and Pharmacological Study of Mongolian Medicine Tonglaga-5 Transdermal Patch(MYYXTPY202313)
OBJECTIVE: To explore the mechanism of Tonglaga-5 (通拉嘎-5, TLG-5) for the treatment of chronic atrophic gastritis (CAG), based on network pharmacology and metabolomics.
METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into six groups (n = 8): control group; model group; teprenone group, and low-, median-, and high- dose TLG-5 groups. The enzyme linked immunosorbent assay (ELISA) was used to measure the expression of pepsinogen Ⅰ (PG Ⅰ), pepsinogen Ⅱ (PG Ⅱ) and gastrin-17 (G-17) in the serum. Hematoxylin and eosin staining were performed to observe the pathological condition. And the network pharmacology was employed to identify the targets and signaling pathways of TLG-5 affecting CAG. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Finally, validation was performed using the “metabolite-gene” interaction network, molecular docking and quantitative real-time polymerase chain reaction (qPCR).
RESULTS: High-dose TLG-5 significantly improved the expression of PG Ⅰ, PGR (PG Ⅰ/ PG Ⅱ) and G-17 (P < 0.05) and inhibited the expression of phosphoinositide-3-kinase regulatory subunit 2, AKT serine/threonine kinase (AKT), hypoxia-inducible factor 1-alpha (HIF-1α) (P < 0.05). Further, high-dose TLG-5 reduced the number of glands was reduced, and fibrosis with oedema and ecchymosis appeared at the base. Overlapping TLG-5 and CAG gene targets produced 270 interactive targets. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that TLG-5 could affect CAG through the predominantly cancer and inflammation-related pathways. Pyrimidine metabolism was identified as a significantly differential pathway in the mechanism of TLG-5 for treating CAG.
CONCLUSIONS: TLG-5 exerts a therapeutic effect on CAG by regulating β-alanine metabolism, pyrimidine metabolism pathways, and inhibiting the PI3K-AKT signaling pathway and HIF-1 signaling pathways.
Ziqi CHENG , Xin DONG , Temuribagen , Caimeng XU , Shaonan HU , Qianwen CHEN , Yuewu WANG , Haibo WANG , Xiaoyu HE , Dan XUE , Peifeng XUE . Exploration of the mechanism of the Mongolian medicine Tonglaga-5 (通拉嘎-5) for the treatment of n-methyl-n′-nitro-n-nitrosoguanidine-induced chronic atrophic gastritis based on network pharmacology and metabolomics[J]. Journal of Traditional Chinese Medicine, 2025 , 45(6) : 1366 -1375 . DOI: 10.19852/j.cnki.jtcm.20250508.001
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