Ginseng-derived GABAFG ameliorates type 2 diabetes mellitus by modulating autophagy-lysosome pathway and gut microbiota

  • J Adv Res. 2025 Jan 4:S2090-1232(25)00003-7. doi: 10.1016/j.jare.2025.01.003.
Meng-Han Qi  1 ,  Hai-Yan Zhang  1 ,  Yun-Yi Hou  1 ,  Ivan Steve Nguepi Tsopmejio  1 ,  Wei Liu  2 ,  Wen-Guang Chang  3 ,  Chen Chen  4 ,  Zi Wang  5 ,  Wei Li  6
Affiliations
  • 1. College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
  • 2. College of Pharmacy, Beihua University, Jilin 132013, China.
  • 3. Institute for Translational Medicine, The Affiliated Hospital, Qingdao University, Qingdao, China.
  • 4. SBMS, Faculty of Medicine, The University of Queensland, Brisbane, Qld, Australia.
  • 5. College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. Electronic address: [email protected].
  • 6. College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China. Electronic address: [email protected].
PMID: 39761869 DOI: 10.1016/j.jare.2025.01.003
Abstract

Introduction: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic Metabolic Disease caused by Insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear.

Objectives: To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment.

Methods: The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput Sequencing and serum metabolomics.

Results: GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the Insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited Apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia.

Conclusion: This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.

Keywords
Autophagy; GABAFG; Ginseng; Gut microbiota; Serum metabolites; Type 2 diabetes mellitus.
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