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Microbiota, co-metabolites, and network pharmacology reveal the alteration of the ginsenoside fraction on inflammatory bowel disease

  • Dandan, Wang (Research Center of Traditional Chinese Medicine, Affiliated Hospital, Changchun University of Chinese Medicine) ;
  • Mingkun, Guo (Research Center of Traditional Chinese Medicine, Affiliated Hospital, Changchun University of Chinese Medicine) ;
  • Xiangyan, Li (Jilin Ginseng Academy, Changchun University of Chinese Medicine) ;
  • Daqing, Zhao (Jilin Ginseng Academy, Changchun University of Chinese Medicine) ;
  • Mingxing, Wang (Research Center of Traditional Chinese Medicine, Affiliated Hospital, Changchun University of Chinese Medicine)
  • Received : 2021.05.05
  • Accepted : 2022.04.11
  • Published : 2023.01.02

Abstract

Background: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD. Methods: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS. Results: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD. Conclusion: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host-flora co-metabolism pathway.

Keywords

Acknowledgement

This work was supported by the National Key Research and Development Program of China [2017YFC1702100], the National Natural Science Foundation of China [81603276, U19A2013 and 82004099], the Department of Science and Technology of Jilin Province [20190101010JH, 20200201419JC and 202002053JC], and the Science and Technology Projects in Jilin Province Department of Education [JJKH20200903KJ]. Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education. Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine.

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