scholarly journals A metabolomics-binding network pharmacology study of Zuojin Pill intervention in chronic atrophic gastritis induced by Helicobacter pylori

2020 ◽  
Author(s):  
Shihua Wu ◽  
Xing Chen ◽  
Honghong Liu ◽  
Ruilin Wang ◽  
Jianyu Li ◽  
...  

Abstract Background Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the mechanism of intervention of ZJP in chronic atrophic gastritis (CAG) through metabolomics combined with network pharmacology.Materials and methods Potential metabolites and possible pathways for ZJP treatment of CAG were explored using a UPLC-Q-TOF/MS-based metabolomics technique. The key targeting mechanism of ZJP for CAG was explored by combining the analysis with network pharmacology.Results ZJP significantly reduced serum levels of IL-1β, IL-6, IL-10 and iNOS, and improved pathological characteristics. Metabolomic results indicated that the therapeutic effect of ZJP was mainly related to ten metabolites, including choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism, butanoate metabolism and purine metabolism. Validation of potential metabolic markers and key targets of network pharmacology by RT-PCR analysis showed that ZJP significantly down-regulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1.Conclusion For the first time, a combination of metabolomics and network pharmacology has been used to clarify the therapeutic effects of ZJP on CAG and its relationship to the regulation of multiple metabolic pathways.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shihua Wu ◽  
Xing Chen ◽  
Honghong Liu ◽  
Ruilin Wang ◽  
Jianyu Li ◽  
...  

Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the therapeutic effects and potential mechanism of ZJP in chronic atrophic gastritis (CAG) through UPLC-Q-TOF/MS-based metabolomics combined with network pharmacology. ZJP and omeprazole significantly reduce contents of IL-1β, IL-6, IL-10, and iNOS and improve pathological characteristics. Metabolomic results indicated that the therapeutic effects of ZJP were mainly related to ten metabolites, namely, choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde, and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; citrate cycle (TCA cycle), alanine, aspartate, and glutamate metabolism; butanoate metabolism; and purine metabolism. Validation of metabolic markers and key targets of network pharmacology through RT-PCR analysis showed that ZJP significantly downregulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1. This study was the first to use a combination of metabolomics and network pharmacology to clarify the therapeutic effects of ZJP on CAG and the regulation of multiple metabolic pathways.


2020 ◽  
Author(s):  
Shihua Wu ◽  
Chunmei Bao ◽  
Ruilin Wang ◽  
Xiaomei Zhang ◽  
Sijia Gao ◽  
...  

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.


Phytomedicine ◽  
2021 ◽  
pp. 153837
Author(s):  
Wuai Zhou ◽  
Huan Zhang ◽  
Xin Wang ◽  
Jun Kang ◽  
Wuyan Guo ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Yameng Zhang ◽  
Chao Li ◽  
Shanmei Sun ◽  
Zhiqun Cao ◽  
Jian Chen ◽  
...  

Chronic atrophic gastritis (CAG) is a common and possibly precancerous digestive tract disease. Development of drugs with effect of preventing precancerous lesions draws the eyes of global researchers. Qilianshupi decoction (QLSP) is a Traditional Chinese Medicine (TCM) that is commonly used to treat CAG, but few studies have explored the mechanism of QLSP on treating CAG. This study investigated the molecular targets of the component herbs of QLSP in preventing precancerous lesions based on network pharmacology. Network pharmacology analysis revealed that the 6 herbs regulated multiple CAG-related genes, among which the most important were cancer-related pathway (apoptosis, p53, and VEGF) and epithelial cell signaling in Helicobacter pylori infection. Further animal experiments showed that the expression of survivin and p53 in precancerous lesions of CAG rats was significantly increased which was suppressed by QLSP. Moreover, telomerase activity was inhibited in precancerous lesions of CAG rats, and telomere length of gastric mucosa was increased, which was reversed by QLSP. Our results suggest that the components of QLSP prevents gastric precancerous lesions through decreasing the expression of survivin and p53 and regulating telomerase activity and telomere length in CAG.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Qi-da He ◽  
Yuan-peng Huang ◽  
Li-bing Zhu ◽  
Jia-cheng Shen ◽  
Lin-yu Lian ◽  
...  

Acupuncture and moxibustion proved to be very effective in chronic atrophic gastritis (CAG). According to the Chinese traditional medicine theory, chronic diseases have an influence on the function of liver and kidney. However, there is little research to demonstrate this theory. This study is aimed at assessing the1H NMR-based metabolic profiling in liver and kidney of CAG rats and comparing the difference between electroacupuncture and moxibustion treatment. Male SD rats were subjected to CAG modeling by intragastric administration of mixture of 2% sodium salicylate and 30% alcohol coupled with compulsive sporting and irregular fasting for 12 weeks and then treated by electroacupuncture or moxibustion at Liangmen (ST 21) and Zusanli (ST 36) acupoints for 2 weeks. A1H NMR analysis of liver and kidney samples along with histopathological examination and molecular biological assay was employed to assess and compare the therapeutic effects of electroacupuncture and moxibustion. CAG brought characterization of metabolomic signatures in liver and kidney of rats. Both electroacupuncture and moxibustion treatment were found to normalize the CAG-induced changes by restoring energy metabolism, neurotransmitter metabolism, antioxidation metabolism, and other metabolism, while the moxibustion treatment reversed more metabolites related to energy metabolism in liver than electroacupuncture treatment. CAG did have influence on liver and kidney of rats. Both of these treatments had good effects on CAG by reversing the CAG-induced perturbation in liver and kidney. For regulating the energy metabolism in liver, the moxibustion played more important role than electroacupuncture treatment.


2018 ◽  
Vol 5 (6) ◽  
pp. 171806
Author(s):  
Shizhe Li ◽  
Tengfei Xu ◽  
Shu Liu ◽  
Zhiqiang Liu ◽  
Zifeng Pi ◽  
...  

In this study, a new network pharmacology approach based on the components absorbed into the blood was used to investigate the pharmacodynamic material basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule ( FXL ) in treating chronic atrophic gastritis (CAG). Initially, we confirmed the components absorbed into the blood by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the network approach, which was based on the results of components absorbed into the blood, was used to analyse the pharmacodynamic material basis and the pharmacologic mechanism of FXL on treating CAG. As a result, 22 absorbed components were found in rat plasma. Given the results of the absorption analysis of the components, eight pathways associated with CAG development were found. The targets linked to these pathways are the drug targets of FXL in CAG treatment. The components associated with these targets are the potential pharmacodynamic material basis and exert synergy in regulating pathways during CAG treatment.


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