Journal of Traditional Chinese Medicine ›› 2025, Vol. 45 ›› Issue (6): 1366-1375.DOI: 10.19852/j.cnki.jtcm.20250508.001

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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

CHENG Ziqi1, DONG Xin1, Temuribagen 2, XU Caimeng1, HU Shaonan1, CHEN Qianwen1, WANG Yuewu1, WANG Haibo1, HE Xiaoyu1, XUE Dan1, XUE Peifeng1()   

  1. 1 Department of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
    2 Department of Orthopedic, Hohhot city Mongolian medicine Hospital of Traditional Chinese Medicine, Hohhot 010110, China
  • Received:2024-12-14 Accepted:2025-03-25 Online:2025-12-15 Published:2025-05-08
  • Contact: Prof. XUE Peifeng, Department of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China. xpfdc153@163.com, Telephone: +86-471-6653132
  • About author:CHENG Ziqi and DONG Xin are co-first authors and contributed equally to this work
  • 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)

Abstract:

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.

Key words: gastritis, atrophic, metabolomics, network pharm-acology, real-time polymerase chain reaction, Tonglaga-5

Cite this article

CHENG Ziqi, DONG Xin, Temuribagen , XU Caimeng, HU Shaonan, CHEN Qianwen, WANG Yuewu, WANG Haibo, HE Xiaoyu, XUE Dan, XUE Peifeng. 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.