Objective To investigate the potential targets and mechanism by which curcumin regulates cholesterol metabolism in intestinal epithelial cells based on both in vivo and in vitro experiments. Methods A high-cholesterol model was established in ApoE^-/- mice fed a high-fat diet, followed by intervention with curcumin, lipid levels in serum were measured. Hematoxylin-eosin (HE) staining was used to observe pathological changes in small intestine tissue. Western blotting was used to detect the protein expressions of low-density lipoprotein receptor (LDLR), NPC1 like intracellular cholesterol transporter 1 (NPC1L1), adenosine triphosphate binding cassette transporters G8 (ABCG8), ABCG5 and liver X receptor α (LXRα) in small intestine tissue. An in vitro high-cholesterol model was constructed in rat intestinal epithelial cells-6 (IEC-6) using cholesterol micelle stimulation. After intervention with curcumin or LXRα inhibitor GSK2033, lipid levels were detected by oil red O staining and immunofluorescence. Transwell experiment was used to detect cholesterol transport. Western blotting and immunofluorescence were used to detect cholesterol metabolism-related protein expressions. Results In vivo experiments showed that 100, 200 mg/kg curcumin caused no damage to small intestine tissue structure of ApoE^-/- mice fed with high-fat diet, and could reduce the body weight and lipid levels in serum of mice (P < 0.05), regulate the expressions of proteins related to cholesterol uptake and intestinal cholesterol excretion (TICE) pathway (P < 0.05, 0.01). The regulation results of protein profile in vitro experiments were consistent with the in vivo model, and curcumin could reduce the lipid levels of intestinal epithelial cells in a high cholesterol environment and inhibit cholesterol transport (P < 0.05, 0.01). After further intervention with LXRα inhibitor GSK2033, there was a significant reversal in intracellular lipid levels and expressions of TICE pathway related proteins such as ABCG5, ABCG8 and NPC1L1 (P < 0.05). Conclusion Intestinal epithelial LXRα is an important target of curcumin for promoting cholesterol efflux and inhibiting cholesterol uptake, thereby contributing to the maintenance of systemic cholesterol homeostasis, and its effects may also involve other regulatory pathways.

curcumin  /  IEC-6 cells  /  small intestine  /  cholesterol metabolism  /  LXRα