Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
PLoS One. 2019 Aug 12;14(8):e0220377. doi: 10.1371/journal.pone.0220377. eCollection 2019.
Troxerutin (TRX) has a beneficial effect on blood viscosity and platelet aggregation, and is currently used for the treatment of chronic varicosity. Recently, TRX can improve lipid abnormalities, glucose intolerance and oxidative stress in high-fat diet-induced metabolic disorders. In this study, we tested the effect of TRX on metabolic syndrome-associated disorders using a non-obese model of metabolic syndrome-the Hereditary Hypertriglyceridaemic rats (HHTg).
Adult male HHTg rats were fed standard diet without or with TRX (150 mg/kg bwt/day for 4 weeks).
Compared to untreated rats, TRX supplementation in HHTg rats decreased serum glucose (p<0.05) and insulin (p<0.05). Although blood lipids were not affected, TRX decreased hepatic cholesterol concentrations (p<0.01) and reduced gene expression of HMGCR, SREBP2 and SCD1 (p<0.01), involved in cholesterol synthesis and lipid homeostasis. TRX-treated rats exhibited decreased lipoperoxidation and increased activity of antioxidant enzymes SOD and GPx (p<0.05) in the liver. In addition, TRX supplementation increased insulin sensitivity in muscles and epididymal adipose tissue (p<0.05). Elevated serum adiponectin (p<0.05) and decreased muscle triglyceride (p<0.05) helped improve insulin sensitivity. Among the beneficial effects of TRX were changes to cytochrome P450 family enzymes. Hepatic gene expression of CYP4A1, CYP4A3 and CYP5A1 (p<0.01) decreased, while there was a marked elevation in gene expression of CYP1A1 (p<0.01).
Our results indicate that TRX improves hepatic lipid metabolism and insulin sensitivity in peripheral tissues. As well as ameliorating oxidative stress, TRX can reduce ectopic lipid deposition, affect genes involved in lipid metabolism, and influence the activity of CYP family enzymes.
曲克芦丁（TRX）对血液黏度和血小板聚集具有有益作用，目前用于治疗慢性静脉曲张。最近，TRX 可以改善高脂肪饮食诱导的代谢紊乱中的血脂异常、葡萄糖不耐受和氧化应激。在这项研究中，我们使用代谢综合征非肥胖模型——遗传性高脂血症大鼠（HHTg）测试了 TRX 对代谢综合征相关疾病的影响。
成年雄性 HHTg 大鼠给予标准饮食或含 TRX（150mg/kg bwt/天，持续 4 周）的饮食。
与未治疗的大鼠相比，TRX 补充剂可降低 HHTg 大鼠的血清葡萄糖（p<0.05）和胰岛素（p<0.05）。尽管血脂没有受到影响，但 TRX 降低了肝胆固醇浓度（p<0.01），并降低了胆固醇合成和脂质稳态相关的 HMGCR、SREBP2 和 SCD1 的基因表达（p<0.01）。TRX 治疗的大鼠肝脏中的脂质过氧化减少，抗氧化酶 SOD 和 GPx 的活性增加（p<0.05）。此外，TRX 补充剂可增加肌肉和附睾脂肪组织的胰岛素敏感性（p<0.05）。升高的血清脂联素（p<0.05）和降低的肌肉甘油三酯（p<0.05）有助于改善胰岛素敏感性。TRX 的有益作用之一是改变细胞色素 P450 家族酶。肝 CYP4A1、CYP4A3 和 CYP5A1 的基因表达降低（p<0.01），而 CYP1A1 的基因表达显著升高（p<0.01）。
我们的结果表明，TRX 可改善肝脏脂质代谢和外周组织的胰岛素敏感性。除了改善氧化应激外，TRX 还可以减少异位脂质沉积，影响参与脂质代谢的基因，并影响 CYP 家族酶的活性。
