Effects of Black Raspberry on Lipid Profiles and Vascular Endothelial Function in Patients with Metabolic Syndrome Han Saem Jeong, 1 Soon Jun Hong, 1 * Tae-Bum Lee, 2 Ji-Wung Kwon, 2 Jong Tae Jeong, 2 Hyung Joon Joo, 1 Jae Hyoung Park, 1 Chul-Min Ahn, 1 Cheol Woong Yu 1 and Do-Sun Lim 1 1 Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea 2 Gochang Black Raspberry Research Institute, Gochang-gun 585-943, Korea Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (À22.8 ± 30.4 mg/dL vs. À1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (À0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL-6 (À0.4 ± 1.5 pg/mL vs. À0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF-α (À2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: black raspberry; metabolic syndrome; lipid; endothelial function; inflammation. INTRODUCTION Black raspberry (Rubus occidentalis) is a member of the Rosaceae family and grows wild in South Korea, Japan, and China. Black raspberry has been used to treat pros- tate and urinary diseases in Korea (Kim et al., 2005). The extract of this plant contains large amounts of vari- ous natural components such as flavonoids, tannins, phenolic acids, organic acids, tyrosol, and resveratrol (Wang and Lin, 2000). These pharmaceutically active components have anti-inflammatory, anti-oxidative, and anti-atherosclerotic effects by inhibiting the forma- tion of activated oxygen molecules and increasing induc- ible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) (Lim et al., 2012; Wallerath et al., 2002; Yang et al., 2008; Zhao et al., 2011). The com- ponents of tyrosol and resveratrol reduce the uptake of oxidized low-density lipoprotein (LDL) by monocytes/ macrophages through the regulation of JNK activation (Bhandary et al., 2012; Vivancos and Moreno, 2008). Resveratrol has been demonstrated to promote vasodi- lation, prevent the oxidation of LDL-cholesterol, and inhibit cholesterol synthesis as polyphenolic compounds (Chen and Pace-Asciak, 1996; Ou et al., 2006; Rakici et al., 2005). The inhibition of the uptake of oxidized LDL is one of the major therapeutic targets of athero- sclerosis (Rader and Daugherty, 2008). The components of metabolic syndrome constitute significant cardiovascular risk factors such as dyslipi- demia, insulin resistance, and inflammation, thereby contributing to atherogenicity (Opie, 2007). However, no prospective randomized study has examined the effects of black raspberry during the early stages of atherosclerosis in high-risk patients. In this regard, the present study investigates the short-term effects of black raspberry on lipid profiles and vascular endothelial func- tion in patients with metabolic syndrome. MATERIALS AND METHODS Study patients. Patients were eligible for this study if they were between 18 and 75 years old with metabolic syndrome. For patients with metabolic syndrome, ≥3 of the following measurements have to be fulfilled: ab- dominal circumference ≥90 cm in men or ≥85 cm in women, triglyceride level ≥150 mg/dL, high-density lipoprotein (HDL) cholesterol <40 mg/dL in men or <50 mg/dL in women, systolic blood pressure ≥130 mm * Correspondence to: Soon Jun Hong, Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 126-1, 5ka, Anam-dong, Sungbuk-ku, Seoul 136-705, Korea. E-mail: psyche94@gmail.com PHYTOTHERAPY RESEARCH Phytother. Res. (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ptr.5154 Copyright © 2014 John Wiley & Sons, Ltd. Received 04 January 2014 Revised 25 February 2014 Accepted 16 March 2014