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Antidiabetic effect of green rooibos (Aspalathus linearis) extract in cultured cells and type 2 diabetic model KK-Ay mice

Abstract

Previous studies have demonstrated antidiabetic effects for rooibos (Aspalathus linearis) and aspalathin (ASP), one of its main polyphenols. Rooibos, an endemic plant of South Africa, is well-known for its use as herbal tea. Green (‘unfermented’) rooibos has been shown to contain more ASP than ‘fermented’ rooibos tea, currently the major product. In the present study, we investigated the antidiabetic effect of green rooibos extract (GRE) through studies on glucose uptake in L6 myotubes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic KK-Ay mice. GRE increased glucose uptake under insulin absent condition and induced phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK) in L6 myotubes as previously demonstrated for ASP. In addition to AMPK, GRE also promoted phosphorylation of Akt, another promoter of glucose transporter 4 (GLUT4) translocation, in L6 myotubes unlike ASP, suggesting an involvement of GRE component(s) other than ASP in Akt phosphorylation. Promotion of GLUT4 translocation to the plasma membrane by GRE in L6 myotubes was demonstrated by Western blotting analysis. GRE suppressed the advanced glycation end products (AGEs)-induced increase in ROS levels in RIN-5F pancreatic β-cells. Subchronic feeding with GRE suppressed the increase in fasting blood glucose levels in type 2 diabetic model KK-Ay mice. These in vitro and in vivo results strongly suggest that GRE has antidiabetic potential through multiple modes of action.

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Abbreviations

AGEs:

Advanced glycation end products

AMPK:

5′-Adenosine monophosphate-activated protein kinase

ASP:

Aspalathin

GLUT4:

Glucose transporter 4

GRE:

Green rooibos extract

HPLC:

High performance liquid chromatography

PPAG:

Phenyl pyruvic acid-2-O-β-glucoside

QROB:

Quercetin-3-O-robinobioside

ROS:

Reactive oxygen species

SB1:

Solvent-based aspalathin-enriched green rooibos extract

STZ:

Streptozotocin

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Acknowledgments

This work was supported by grants to K. Y. and Y. M. from the Japan Society for the Promotion of Science (JSPS) and by grants to E. J. from the National Research Foundation of South Africa (NRF) under the NRF/JSPS (SA/Japan) Scientific Cooperation Agreement. NRF grant holder (E.J.) acknowledges that opinions, findings and conclusions or recommendations expressed in any publication generated by the NRF supported research (Grants 75425 and 85105) are those of the authors, and that the NRF accepts no liability whatsoever in this regard.

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The authors declare that they have no conflict of interest.

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Correspondence to Kazumi Yagasaki.

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Kamakura, R., Son, M.J., de Beer, D. et al. Antidiabetic effect of green rooibos (Aspalathus linearis) extract in cultured cells and type 2 diabetic model KK-Ay mice. Cytotechnology 67, 699–710 (2015). https://doi.org/10.1007/s10616-014-9816-y

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  • DOI: https://doi.org/10.1007/s10616-014-9816-y

Keywords

  • AMPK
  • GLUT4
  • Hyperglycemia
  • L6 myotube
  • RIN-5F cell
  • Rooibos