Hypoglycemic activity and constituents analysis of blueberry (Vaccinium corymbosum) fruit extracts

Abstract

Background

To investigate hypoglycemic activity and elucidate the active composition of the fruit blueberry (Vaccinium corymbosum).

Methods

Methanol extracts of blueberry (MEB) were separated using a D101 macroporous resin column to yield quinic acid derivative (Fr.1)- and flavonoid (Fr.2)-rich fractions. The effects of the blueberry extracts on mRNA expression of GLUT-2 (glucose transporter type 2) and PPARγ (peroxisome proliferator-activated receptor-γ), as well as on the activities of PPRE (peroxisome proliferator response element) and NF-κB were analyzed in LO2 normal liver cells. Real-time PCR was used to detect the expression of GLUT-2, PPARγ, TNF-α, IL-1β, and IL-6 mRNA. The PPRE and NF-κB activities were detected by a luciferase reporter assay. Western blotting was used to detect the levels of PPARγ, GLUT-2, and p65. The active compositions were isolated using various chromatography columns, and were analyzed by NMR.

Results

mRNA and protein expression of GLUT-2 and PPARγ were significantly increased upon treatment with 400 μg/mL extracts of blueberry (P<0.05). The PPRE activity was also significantly increased in a dose-dependent manner upon administration of MEB (P<0.05). Furthermore, the NF-κB activity induced by lipopolysaccharides was inhibited by MEB (P<0.05). No fraction separated from MEB exhibited PPRE activation or NF-κB inhibition activity. Blueberry extract may execute its hypoglycemic activity by stimulating expression of GLUT-2 and PPARγ, and by inhibiting the inflammatory pathway. Together, quinic acid derivatives and flavonoids may result in a synergistic effect. Fourteen phenolic acids, including eight flavonoids, four quinic acid derivatives, and two other phenolic acids, were isolated and identified, and caffeoylquinic acid derivatives and quercetin glycosides were found to be the major constituents of blueberry.

Conclusion

Blueberry may have hypoglycemic activity that functions through synergistic effects with caffeoylquinic acid derivatives and quercetin glycosides.

Keywords:

• blueberry
• hypoglycemic activity
• liver cells
• caffeoylquinic acid derivatives
• fla-vonoids
• synergistic effect

Acknowledgments

The project was supported by the National Natural Science Foundation of China (31500286) and the Natural Science Foundation of Jiangxi Province (20161BAB214167). We thank Nature Research Editing Service for its linguistic assistance during the preparation of this manuscript.

Author contributions

Weifeng Huang and Chunpeng Wan conceived and designed the experiments; Liangliang Yao, Xiao He, Lei Wang, Mingxi Li, and Youxin Yang performed the experiments; Weifeng Huang and Chunpeng Wan analyzed the data; Chunpeng Wan contributed reagents/materials/analysis tools; Weifeng Huang and Chunpeng Wan wrote the paper. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.