Hypocholesterolemic Activity of Curcumin Is Mediated by Down-regulating the Expression of Niemann-Pick C1-like 1 in Hamsters
Hypocholesterolemic Activity of Curcumin Is Mediated by Down-regulating the Expression of Niemann-Pick C1-like 1 in Hamsters
复制标题
姜黄素的降胆固醇活性是通过下调仓鼠中 Niemann-Pick C1-like 1 的表达介导的
DOI：
10.1021/acs.jafc.6b04102
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发表时间：
2017-01-18
影响因子：
6.1
通讯作者：
Lui, Minqi
中科院分区：
文献类型：
--
作者：
Feng, Dan;Zou, Jun;Lui, Minqi
我们以前证明，姜黄素通过下调尼曼-匹克Cl样1（NPC 1 L1）表达降低Caco-2细胞中的胆固醇吸收，但姜黄素对肠道胆固醇吸收的体内作用仍然未知。本研究旨在探讨姜黄素摄入对仓鼠胆固醇吸收的影响及其机制。雄性仓鼠喂食高脂肪饮食，补充或不补充姜黄素（0.05% w/w），持续12周。姜黄素补充显著降低血清总胆固醇（TC）（从6.86 +/- 0.27至3.50 +/- 0.24 mmol/ L），甘油三酯（TG）（从5.07 +/- 0.34至3.72 +/- 0.40 mmol/L），和低密度脂蛋白胆固醇（从2.58 +/- 0.19至1.71 +/- 0.15 mmol/L）水平以及肝脏TC（从11.6 +/- 0.05至7.2 +/- 0.03 mg/g）和TG（从30.3 +/- 0.22至25.2 +/- 0.18 mg/g）水平（所有P < 0.05）。相反，姜黄素治疗显著增加粪便胆固醇排出量（P < 0.01）。此外，姜黄素还能显著下调小肠中固醇调节元件结合蛋白2（SREBP-2）和NPC 1 L1的mRNA和蛋白表达（P < 0.05）。我们目前的研究结果表明，姜黄素通过抑制SREBP-2和随后下调NPC 1 L1表达来抑制仓鼠的胆固醇吸收，这可能是姜黄素降胆固醇作用的原因。
We previously demonstrated that curcumin reduces cholesterol absorption in Caco-2 cells through down regulating Niemann-Pick Cl-like 1 (NPC1L1) expression, but the in vivo effect of curcumin on intestinal cholesterol absorption remains unknown. The present study aimed to investigate the effects and mechanisms of curcumin consumption on cholesterol absorption in hamsters. Male hamsters were fed a high-fat diet supplemented with or without curcumin (0.05% w/w) for 12 weeks. Curcumin supplementation significantly decreased serum total cholesterol (TC) (from 6.86 +/- 0.27 to 3.50 +/- 0.24 mmol/ L), triglyceride (TG) (from 5.07 +/- 0.34 to 3.72 +/- 0.40 mmol/L), and low-density lipoprotein cholesterol (from 2.58 +/- 0.19 to 1.71 +/- 0.15 mmol/L) levels as well as liver TC (from 11.6 +/- 0.05 to 7.2 +/- 0.03 mg/g) and TG (from 30.3 +/- 0.22 to 25.2 +/- 0.18 mg/g) levels (P < 0.05 for all). In contrast, curcumin treatment markedly enhanced fecal cholesterol output (P < 0.01). Moreover, curcumin supplementation down-regulated the mRNA and protein expressions of sterol regulatory element binding protein-2 (SREBP-2) and NPC1L1 in the small intestine (P < 0.05). Our current results indicate that curcumin inhibits cholesterol absorption in hamsters by suppressing SREBP-2 and subsequently down-regulating NPC1L1 expression, which may be responsible for the hypocholesterolemic effects of curcumin.