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 ran...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 pepsinogenⅠ(PGⅠ),pepsinogenⅡ(PGⅡ)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(q PCR).RESULTS:High-dose TLG-5 significantly improved the expression of PGⅠ,PGR(PGⅠ/PGⅡ)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 regulatingβ-alanine metabolism,pyrimidine metabolism pathways,and inhibiting the PI3K-AKT signaling pathway and HIF-1 signaling pathways.展开更多
基金the National Natural Science Foundation of China:New Quality Control Model of Mongolian Medicine Tonglaga-5“Qingzhuo Shenghua”Based on“Stomach Blood Bone Correlation Tracking”(No.82160745)Grassland Talent Rolling Support Program([2023]3)+1 种基金Key Projects of Inner Mongolia Medical University:Research on the Mechanism of Mongolian Prescription Tonglaga-5 in Treating Chronic Atrophic Gastritis based on Multiomics Integration(No.YKD2024ZD001)Scientific Research Projects of the Inner Mongolia Autonomous Region Collaborative Innovation Centre of Mongolian Medicine:Preparation and Pharmacological Study of Mongolian Medicine Tonglaga-5 Transdermal Patch(No.MYYXTPY202313)。
文摘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 pepsinogenⅠ(PGⅠ),pepsinogenⅡ(PGⅡ)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(q PCR).RESULTS:High-dose TLG-5 significantly improved the expression of PGⅠ,PGR(PGⅠ/PGⅡ)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 regulatingβ-alanine metabolism,pyrimidine metabolism pathways,and inhibiting the PI3K-AKT signaling pathway and HIF-1 signaling pathways.
