Hye Ran Choi

Effects of Extracts of Unripe Black Raspberry and Red Ginseng on Cholesterol Synthesis

We investigated the effects of water extracts of unripe black raspberry (UBR) and red ginseng (RG) on cholesterol synthesis, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and expression of low-density lipoprotein (LDL) or high-density lipoprotein (HDL)-related genes in HepG2 and Caco-2 (human hepatoma and intestinal cell lines, respectively). Our results showed that cholesterol synthesis and HMG-CoA reductase activity in HepG2 cells were inhibited by UBR and RG. Further, co-treatment with UBR and RG had a greater effect than did treatment with either UBR or RG. In Caco-2 cells, treatment with UBR and RG increased the expression of LDL-regulated genes, such as LDL receptor and SREBP-2, and also upregulated the level of HDL-associated ABCA1. Moreover, co-treatment with UBR and RG appeared to be more effective than treatment with either UBR or RG. Taken together, our results indicate that UBR and RG regulate the level of HDL-associated ABCA1 via signaling pathway, thereby preventing cholesterol synthesis.

Improvement of Cholesterol and Blood Pressure in Fruit, Leaf and Stem Extracts from Black Raspberry in vitro

We compared effects of fruit, leaf, and stem extracts from black raspberry on improvement of cholesterol and blood pressure in HepG2 and HUVEC cells, respectively. Cholesterol secretion was inhibited by water extracts of unripe fruit and stem, but not leaf of black raspberry in HepG2 cells. Also, water extracts of unripe fruit, leaf, and stem reduced HMG-CoA reductase activity. Furthermore, nitric oxide production and expression of angiotensin-converting enzyme (ACE) protein were regulated by extracts of fruit, leaf, and stem of black raspberry in HUVEC cells. Overall, the rank order according to the improving level of cholesterol and hypertension is as follows: stem > fruit > leaf. In addition, various polyphenol compounds displayed inhibitory effects of HMG-CoA reductase activity and ACE expression. Thus, these data suggested that leaf and stem as wells as fruit of black raspberry can be used as useful food resources for reduction of cholesterol and blood pressure.

Blood Pressure Modulating Effects of Black Raspberry Extracts in vitro and in vivo

This study aimed to investigate the effects of 50% ethanol extract of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in human umbilical vein endothelial cells (HUVECs) and in spontaneously hypertensive rats (SHR). Angiotensin converting enzyme (ACE) inhibition and activation of nitric oxide production by endothelial nitric oxide synthase were significantly regulated by RBR in HUVEC cells. Moreover, the SHR showed significantly higher levels of blood pressure, ACE, renin, endothelin-1, and interleukin-6 than Wistar Kyoto rats (WKY). However, treatment with captopril and RBR decreased the levels of these hypertension-related events in the SHR. The renal arteriole showed greater media thickness/lumen diameter (%) in the SHR than in the WKY. However, media thickness/lumen diameter (%) was reduced in SHR by treatment with captopril and RBR. In addition, the number of eosinophilic cardiac muscle cells was decreased in the heart muscles after treatment with captopril and RBR. Therefore, this study suggests that 50% ethanol extract of RBR may be useful for the prevention and treatment of high blood pressure.

The Anti-aging Effects of Various Berries in the Human Skin Keratinocyte (HaCaT) Cells

Su Jung Lee, Hye Ran Choi, Jin-Cheol Lee, Hee Jeon Park, Hee Kwon Lee, Jong Tae Jeong, and Tae-Bum Lee*Gochang Black Raspberry Research InstituteAbstract Ultraviolet B (UV-B) irradiation is a negative factor that induces skin damage, inflammation, and aging. UV-B irradiation induces the inflammatory response through interleukin (IL)-6 and IL-8 expression in keratinocytes. Inaddition, it induces the production of reactive oxygen species (ROS) and the activation of matrix metalloproteinase-1(MMP-1), which plays an important role in collagen 1 degradation in the extracellular matrix. We investigated the anti-aging effects of five kinds of berry in human skin keratinocyte (HaCaT) cells using juice of black raspberry (Rubusoccidentalis), blueberry wild (Vacciniun angustifolium) and cultivar (Vacciniun corymbosum), black chokeberry (Aroniamelanocarpa (Michx.) Elliott), and mulberry (Morus abla). HaCaT cells irradiated with UV-B exhibited increased ROSgeneration, as well as IL-6, IL-8, and MMP-1 gene expression, when compared to the control cells that were not irradiatedwith UV-B. However, pre-treatment of berry juice before UV-B irradiation significantly down-regulated the UV-B-inducedROS generation and inflammatory cytokine and MMP-1 expression. The results suggest that all berries have anti-agingeffects including lowering inflammatory cytokine levels, ROS generation, and MMP-1 expression in HaCaT cells duringUV-B irradiation.Keywords: berry, ultraviolet B, inflammatory cytokine, reactive oxygen species, matrix metalloproteinase-1

Effects of Unripe Black Raspberry Water Extract on Lipid Metabolism and Oxidative Stress in Mice

Hye Ran Choi, Jung-Hyun Lee, Su Jung Lee, Min Jung Lee, Jong Tae Jeong, and Tae-Bum Lee*Gochang Black Raspberry Research InstituteAbstract We examined the effects of unripe black raspberry water extract (UBR-W) on lipid metabolism and oxidativestress in mice. C57BL/6J mice were divided into 4 groups: those administered a control diet (CTL), high-fat diet (HFD),UBR-W and simvastatin for 12 weeks. In the HFD group, LDL cholesterol were significantly higher than in the CTLgroup. However, the UBR-W treated group showed dose-dependent reduction of plasma LDL levels. Hepatic total lipid,TC, and malondialdehyde were significantly increased in hyperlipidemic mice. However, supplementation with either UBR-W or simvastatin effectively reduced these lipid profiles and lipid peroxidation. UBR-W increased mRNA expression ofthe LDL receptor, sterol regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl (HMG)-CoAreductase and ATP-binding cassette transporter A1 (ABCA1) compared to that observed in the HFD group. In addition,UBR-W and simvastatin showed significantly reduced oxidized LDL uptake by the scavenger receptor CD36. These resultssuggest that UBR-W is useful for treatment and prevention of hyperlipidemia and lipid peroxidation.Keywords: Unripe black raspberry, High-fat diet, Hyperlipidemia, Lipid metabolism, Oxidative stress

Characterization of Lactobacillus plantarum strains isolated from black raspberry and their effect on BALB/c mice gut microbiota

The objective of this study was to evaluate probiotic effects of two Lactobacillus plantarum strains (GBL16 and 17) isolated from black raspberry. Results revealed that the number of GBL16 was gradually decreased as bile salt concentration was increased from 0.3 to 1%. However, GBL17 did not show any difference when GBL17 was applied to 1% bile salt, and it indicates that GBL17 is more tolerant to bile salt than GBL16. GBL17 exhibited higher heat resistance and adhesion ability to Caco-2 cells than GBL16. Regarding gut microbiome, no significant change in the number of total bacteria in intestines of mice after treatment with GBLs was determined. However, the combination of GBL16 and GBL17 significantly increased the number of total bacteria in intestines of mice after they were orally administered. Therefore, the results suggest that both GBL16 and 17 strains could be one of major probiotics that can improve human gut health.

Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice.

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.