关键词: 8-hydroxydeoxyguanosine HbA1c hesperidin insulin metabolic syndrome

Mesh : Animals Hesperidin / pharmacology Oxidative Stress / drug effects Insulin Resistance Metabolic Syndrome / drug therapy metabolism Male Mice Citrus / chemistry Mice, Inbred C57BL Dietary Supplements Disease Models, Animal Dose-Response Relationship, Drug Blood Glucose / metabolism drug effects Diet, High-Fat / adverse effects Antioxidants / pharmacology

来  源:   DOI:10.3390/biom14060637   PDF(Pubmed)

Abstract:
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.
摘要:
代谢综合征(MetS)是一组代谢异常,影响约25%的成年人,与心血管疾病等慢性疾病有关。癌症,和神经退行性疾病。氧化应激和炎症是MetS的关键驱动因素。橙皮苷,柑橘生物类黄酮,已经证明了抗氧化和抗炎特性;然而,其对MetS的影响尚未完全确定。我们旨在确定改善氧化应激所需的橙皮苷的最佳剂量,全身性炎症,在MetS的新型小鼠模型中进行血糖控制。雄性5周龄C57BL/6小鼠饲喂高脂肪,高盐,高糖饮食(HFSS;食物和饮用水中42%千卡脂肪含量,含0.9%盐水和10%高果糖玉米糖浆)16周。HFSS治疗6周后,小鼠被随机分配到安慰剂组或低(70毫克/千克/天),中期(140毫克/千克/天),或高剂量(280mg/kg/天)橙皮苷补充12周。HFSS饮食引起显著的代谢紊乱。HFSS+安慰剂小鼠的体重增加了对照小鼠的几乎两倍(p<0.0001)。空腹血糖(FBG)增加了40%(p<0.0001),血浆胰岛素100%(p<0.05),HOMA-IR下降150%(p<0.0004),表明胰岛素抵抗。在140mg/kg/天(p<0.0001)和280mg/kg/天(p<0.005)时,补充橙皮苷使血浆胰岛素降低40%。HOMA-IR在两种剂量下都降低了45%(p<0.0001)。血浆橙皮苷水平在所有橙皮苷组中显著升高(p<0.0001)。氧化应激,用8-OHdG测量,在HFSS饮食小鼠中增加了40%(p<0.001),在所有橙皮苷剂量下减少了20%(p<0.005)。总之,补充橙皮苷可降低HFSS喂养小鼠的胰岛素抵抗和氧化应激,证明其在MetS中的剂量依赖性治疗潜力。
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