4.7 Article

Synergistic Effects of Combined Anthocyanin and Metformin Treatment for Hyperglycemia In Vitro and In Vivo

Journal

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 70, Issue 4, Pages 1182-1195

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c07799

Keywords

anthocyanins; insulin resistance; gut microbiota; metformin; hypoglycemic effect

Funding

  1. National Natural Science Foundation of China [U21A20273]
  2. First Batch of Liaoning Unveiling Leader Scientific and Technological Projects [2021JH1/10400036]
  3. China Agriculture Research System of MOF [CARS-29]
  4. Liaoning Province Doctoral Research Startup Fund Project [2019-BS-205]
  5. Scientific research fund project of Liaoning Provincial Department of Education [LSNQN201915]
  6. Scientific Research Foundation of Shenyang Agricultural University [880418027]
  7. China Agriculture Research System of MARA [CARS-29]

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The simultaneous use of metformin and anthocyanin-rich foods has a synergistic effect in reducing blood glucose levels and improving insulin resistance in diabetic patients. The combination treatment also regulates signaling pathways and alters gut microbial composition, leading to enhanced therapeutic efficacy.
The mechanism underlying the hypoglycemic effect of the simultaneous use of metformin and anthocyanin-rich foods is not yet clear. Hence, the effects and possible mechanisms of action of these substances, alone and in combination, were evaluated in insulin-resistant HepG2 cells and a diabetic mouse model. The results indicated that anthocyanin and metformin had a significant synergistic effect on glucose consumption (CI < 0.9) compared with metformin alone in HepG2 cells. In the mouse model, combined treatment (50 and 100 mg/kg metformin + anthocyanin groups) demonstrated synergistic restorative effects on the blood glucose level, insulin resistance, and organ damage in the liver, pancreas, and ileum. Additionally, combined metformin and anthocyanin treatment suppressed protein tyrosine phosphatase 1B expression and regulated the PI3K/AKT/GSK3 beta pathway. Combined treatment also altered the gut microbial composition and structure by increasing the relative abundance of beneficial bacteria and the short-chain fatty acid content. These results suggest that the use of anthocyanins can enhance the efficacy of metformin treatment for hyperglycemia and provide a reference for further clinical research regarding nutrition and supplementary treatment.

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