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1H-NMR and MS Based Metabolomics Study of the Intervention Effect of Curcumin on Hyperlipidemia Mice Induced by High-Fat Diet

机译:1H-NMR和MS的代谢组学研究姜黄素对高脂饮食诱导的高脂血症小鼠的干预作用

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摘要

Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.
机译:姜黄素是姜黄的主要生物活性成分,以其抗高血脂作用而闻名。但是,目前尚无姜黄素在高脂血症模型上的整体代谢信息,这可能为我们提供了对潜在机制的了解。在目前的工作中,进行了基于NMR和MS的代谢组学研究,研究姜黄素对高脂饮食(HFD)喂养12周所致高脂血症小鼠的干预作用。在诱导期间,每天一次对HFD诱导的动物口服姜黄素(40,80 mg / kg)或洛伐他汀(30 mg / kg,阳性对照)。进行了TC,TG,LDL-c和HDL-c的血清生化分析,结果证明姜黄素或洛伐他汀的治疗可以显着改善血脂水平。随后,对尿液样本进行了代谢组学分析。正交偏最小二乘判别分析(OPLS-DA)用于研究姜黄素的抗高脂血症作用并检测相关的潜在生物标志物。总共鉴定出35个生物标志物,其中NMR鉴定了31个,MS鉴定了9个(两者均5个)。事实证明,姜黄素治疗可以部分恢复由HFD引起的代谢紊乱,涉及以下代谢途径:TCA循环,糖酵解和糖异生,酮体和胆固醇的合成,支链氨基酸的生酮,胆碱代谢和脂肪酸代谢。此外,基于NMR和MS的代谢组学被证明是研究天然产物的药效学作用和潜在机理的有力工具。

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