In vitro and in vivo studies on the effects of red raspberries (Rubus ideaus L.) on biomarkers of diabetes mellitus and associated metabolic disorders

The study aimed to determine the effects of red raspberries (Rubus ideaus L.) on biomarkers of diabetes (DM) and associated metabolic disorders including oxidative stress, inflammation and cardiovascular risk factors using in vitro and in vivo studies. The study has three sections that included 1) characterization of the polyphenols in red raspberries; 2) in vitro study on the effects of red raspberry crude extracts (RCE) on biomarkers of oxidative stress and inflammation in glucose-induced hyperglycemia in human umbilical vein endothelial cells (HUVECs) that mimicked hyperglycemia in DM; and 3) in vivo study on the effects of 9.75% red raspberry supplementation on biomarkers of DM and DM-induced metabolic disorders using obese diabetic (db/db) mice. Results showed that red raspberries contain polyphenols such as quercetin and flavonoids which are known as the most potent antioxidants and ellagic acid which has anti-proliferative property. In vitro study showed that RCE significantly reduced reactive oxygen species (ROS) and lipid peroxidation in glucose-induced hyperglycemia in HUVECs. At high concentration, RCE behave as pro-oxidant and significantly decreased cell proliferation. Furthermore, RCE modulated the gene expression of transcription factors, Nrf2 and PPAR-gamma, that regulate oxidative stress and inflammation. Moreover, it significantly down-regulated the gene expression of pro-inflammatory transcription factor NF-kB and cytokine IL-6 in dose-dependent manner. In vivo study revealed that 9.75% red raspberry supplementation attenuated oxidative stress in obese db/db mice. It significantly reduced the levels of ROS and enhanced the activity of antioxidant enzyme, glutathaione peroxidase (GPx), in blood and liver at p-value 0.05. For most biomarkers, reduced levels were noted in red raspberry-supplemented groups but the differences with the control group failed to reach significance. The characteristics of mouse model, the complex biological system of in vivo and the complex nature of test food might have confounded the results, thus, serve as noteworthy considerations for future studies. In vitro and in vivo data showed that red raspberries attenuate oxidative stress related to DM by inhibiting ROS and lipid peroxidation as well as increasing antioxidant enzyme GPx. Studies focused on metabolomics, signalling pathways and molecular targets using varying doses and varieties of raspberries merit further investigations.