College of Food, Shenyang Agricultural University, Shenyang, Liaoning, China.
J Med Food. 2012 May;15(5):495-503. doi: 10.1089/jmf.2011.1717.
The protective effect of raspberry ketone against nonalcoholic steatohepatitis (NASH) was tested by using a high-fat diet-induced NASH model, and its mechanism was explored. Forty Sprague-Dawley rats with a 1:1 male to female ratio were randomly divided into five groups: the normal control (NC) group (n=8) fed normal diet for 8 weeks, the model control (MC) group (n=8) fed high-fat diet (82% standard diet, 8.3% yolk powder, 9.0% lard, 0.5% cholesterol, and 0.2% sodium taurocholate), and the raspberry ketone low-dose (0.5%) (RKL) group (n=8), the raspberry ketone middle-dose (1%) (RKM) group (n=8), and the raspberry ketone high-dose (2%) (RKH) group (n=8) fed high-fat diet for 4 weeks. After 8 weeks of experiment, all the rats were sacrificed, and blood lipid parameters (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]), liver function parameters (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]), leptin (LEP), free fatty acid (FFA), tumor necrosis factor α (TNF-α), blood glucose (GLU), and insulin (INS) with calculated INS resistance index (IRI) and INS-sensitive index (ISI) were measured in rats. Therefore, we determined the peroxisome proliferator-activated receptor (PPAR)-α activity in liver homogenate and the levels of low-density lipoprotein receptor (LDLR), high-sensitivity C-reactive protein (hs-CRP), adiponection (APN), superoxide dismutase, and malondialdehyde (MDA). The liver tissues of rats in each group were imaged by electron microscopy with hematoxylin-eosin as the staining agent. The levels of TG, TC, LDL-C, ALT, AST, ALP, GLU, INS, IRI, FFA, LEP, TNF-α, MDA, and hs-CRP of MC rats were significantly increased (P<.05, P<.01). Therefore, the levels of HDL-C, ISI, PPAR-α, LDLR, and APN were significantly decreased (P<.05, P<.01). Compared with the MC group, each parameter in the RKL, RKM, and RKH groups was significantly improved (P<.05, P<.01). Thus raspberry ketone was an effective intervention for NASH in rats. It was believed that raspberry ketone had a dual effect of liver protection and fat reduction, and the mechanism was probably mediated by alleviation of fatty degeneration of liver cells, decreased liver inflammation, correction of dyslipidemia, reversal of LEP and INS resistance, and improved antioxidant capacity.
采用高脂饮食诱导非酒精性脂肪性肝炎（NASH）模型，研究覆盆子酮对 NASH 的保护作用，并探讨其作用机制。40 只雌雄各半的 Sprague-Dawley 大鼠随机分为 5 组：正常对照组（NC 组，n=8）给予普通饮食 8 周，模型对照组（MC 组，n=8）给予高脂饮食（82%标准饮食、8.3%蛋黄粉、9.0%猪油、0.5%胆固醇、0.2%牛磺胆酸钠），以及覆盆子酮低剂量（0.5%）（RKL）组（n=8）、覆盆子酮中剂量（1%）（RKM）组（n=8）和覆盆子酮高剂量（2%）（RKH）组（n=8），给予高脂饮食 4 周。实验 8 周后，所有大鼠均处死，检测血脂参数（总胆固醇[TC]、甘油三酯[TG]、高密度脂蛋白胆固醇[HDL-C]、低密度脂蛋白胆固醇[LDL-C]）、肝功能参数（血清丙氨酸氨基转移酶[ALT]、天门冬氨酸氨基转移酶[AST]、碱性磷酸酶[ALP]）、瘦素（LEP）、游离脂肪酸（FFA）、肿瘤坏死因子-α（TNF-α）、血糖（GLU）和胰岛素（INS），并计算胰岛素抵抗指数（IRI）和胰岛素敏感指数（ISI）。因此，我们测定了肝匀浆过氧化物酶体增殖物激活受体（PPAR）-α活性以及低密度脂蛋白受体（LDLR）、高敏 C 反应蛋白（hs-CRP）、脂联素（APN）、超氧化物歧化酶和丙二醛（MDA）水平。各组大鼠肝组织采用苏木精-伊红染色剂进行电镜成像。MC 大鼠的 TG、TC、LDL-C、ALT、AST、ALP、GLU、INS、IRI、FFA、LEP、TNF-α、MDA 和 hs-CRP 水平明显升高（P<.05，P<.01）。因此，HDL-C、ISI、PPAR-α、LDLR 和 APN 水平明显降低（P<.05，P<.01）。与 MC 组相比，RKL、RKM 和 RKH 组的各参数均有明显改善（P<.05，P<.01）。因此，覆盆子酮是大鼠 NASH 的有效干预药物。我们认为覆盆子酮具有肝脏保护和减脂的双重作用，其机制可能与减轻肝细胞脂肪变性、降低肝炎症、纠正血脂异常、逆转 LEP 和胰岛素抵抗、改善抗氧化能力有关。
