Hypocholesterolemic Activity of Curcumin Is Mediated by Down-regulating the Expression of Niemann-Pick C1-like 1 in Hamsters

J Agric Food Chem. 2017 Jan 18;65(2):276-280. doi: 10.1021/acs.jafc.6b04102. Epub 2017 Jan 3.

Abstract

We previously demonstrated that curcumin reduces cholesterol absorption in Caco-2 cells through down-regulating Niemann-Pick C1-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.

Keywords: Niemann-Pick C1-like 1; cholesterol absorption; curcumin; hamsters; sterol regulatory element binding protein-2.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Body Weight / drug effects
  • Cholesterol / metabolism
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects
  • Eating / drug effects
  • Feces
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption / drug effects
  • Lipids / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mesocricetus
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism

Substances

  • Anticholesteremic Agents
  • Lipids
  • Membrane Transport Proteins
  • Sterol Regulatory Element Binding Protein 2
  • Cholesterol
  • Curcumin