Inhibitory effect of black raspberry extract on AGE accumulation and degradation, and ROS production in HUVEC cells


  • Katsuaki Dan Research Organization of Biological Activity
  • Atsushi Takada
  • Yasunori Kanaho
  • Yuko Kusumi
  • Harutaka Banno



Background: A critical event in age-related diseases involves the glycation of various proteins in the animal body to generate advanced glycation end products (AGEs). We have previously found that black raspberry extract (BRE) has effects on age-related diseases. From this observation, we expected that berry extracts, specifically BRE, would have positive effects on AGE-stimulated cell events that link to age-related diseases.

Objective: To discuss the potency of berry extracts against diseases attributable to the AGE-dependent changes of cellular events, in this study, we examined the effects of berry extracts on the cellular events changed upon AGE stimulation of human umbilical vein endothelial cells (HUVECs) through AGE receptors.

Methods: After HUVECs were incubated with AGE-BSA in the presence of serially diluted berry extracts, mRNA and protein levels of AGE receptors, intracellular AGE accumulation, and ROS production in the cell were determined by qRT-PCR and Western blotting, ELISA, and staining with the fluorescent probe, respectively.

Results: Although concentration-dependent effects of berry extracts tested on mRNA levels of AGE receptors in HUVECs were not clear, mRNA level of the AGE receptor RAGE that is involved in the intracellular ROS production was increased by Blabina, which contains BRE, and the well-known anti-glycation compound aminoguanidine (AGD). In contrast, the protein expression level of RAGE was decreased by BRE and Blabina, but not by AGD. It was also found that BRE and Blabina suppressed AGE-BSA-stimulated ROS production in HUVECs. The extent of inhibition in the RAGE protein expression by BRE and Blabina was correlated well with the ROS generation measured in these samples.

Conclusions: The results obtained in this study demonstrate that BRE has the most potent inhibitory effect on ROS accumulation in the cell, probably due to the suppression in the expression level of the RAGE protein. These observations suggest that black raspberry could be a potential nutraceutical to prevent various age-related diseases.

Keywords: AGEs; RAGE; ROS; black raspberry; HUVECs.






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