Li Ze-Yun, Ding Li-Li, Li Jin-Mei, Xu Bao-Li, Yang Li, Bi Kai-Shun, Wang Zheng-Tao
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
PLoS One. 2015 Mar 18;10(3):e0120950. doi: 10.1371/journal.pone.0120950. eCollection 2015.
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.
姜黄素是姜黄的主要生物活性成分,以其抗高脂血症作用而闻名。然而,姜黄素对高脂血症模型的整体代谢信息尚未揭示,这可能为我们深入了解其潜在机制提供线索。在本研究中,采用基于核磁共振(NMR)和质谱(MS)的代谢组学方法,研究姜黄素对高脂饮食(HFD)喂养12周诱导的高脂血症小鼠的干预作用。在诱导期,对高脂饮食诱导的动物每天口服一次姜黄素(40、80mg/kg)或洛伐他汀(30mg/kg,阳性对照)。进行了血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)的生化检测,结果证明姜黄素或洛伐他汀治疗可显著改善血脂谱。随后,对尿液样本进行了代谢组学分析。采用正交偏最小二乘判别分析(OPLS-DA)研究姜黄素的抗高脂血症作用并检测相关潜在生物标志物。共鉴定出35个生物标志物,其中通过NMR鉴定出31个,通过MS鉴定出9个(两者均鉴定出5个)。结果表明,姜黄素治疗可部分恢复高脂饮食诱导的代谢紊乱,涉及以下代谢途径:三羧酸循环、糖酵解和糖异生、酮体和胆固醇合成、支链氨基酸生酮作用、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药效学作用及其潜在机制的有力工具。