Dietary curcumin prevents hypercholesterolemia by inhibiting the transcriptional activity of SREBP-2 and HNF1α and reducing intestinal and hepatic NPC1L1 expression in high-fat diet-fed hamsters.
Background: Niemann-Pick C1-like 1 (NPC1L1) mediates cholesterol absorption and plays major roles in cholesterol homeostasis. Our previous study showed that curcumin reduced NPC1L1 expression and cholesterol absorption in Caco-2 cells. This study aimed to investigate whether curcumin could prevent h...
| Publicado en: | Nutrition & Metabolism Vol. 22; no. 1; pp. 1 - 16 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
BioMed Central
10/28/2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=188948376&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 188948376 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17437075 1CYX jtl: Nutrition & Metabolism issn: 17437075 maglogo: N pubinfo: dt: 10/28/2025 vid: 22 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 188948376 188948376 188948376 10.1186/s12986-025-01031-x 188948376 ppf: 1 ppct: 15 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Dietary curcumin prevents hypercholesterolemia by inhibiting the transcriptional activity of SREBP-2 and HNF1α and reducing intestinal and hepatic NPC1L1 expression in high-fat diet-fed hamsters. aug: au: Cao, Zhuo Yang, Jie Mai, Haiyan Hong, Ting Chen, Xiaobing Feng, Dan affil: https://ror.org/0064kty71 Department of Nutrition, School of Public Health, Sun Yat-sen University, 510080, Guangzhou, China sug: subj: Curcumin Therapeutic Use Curcumin Pharmacodynamics Dietary Supplementation Hypercholesterolemia Prevention and Control Transcription Factors Proteins Metabolism Cholesterol Metabolism Dietary Fats Gene Expression Animal Studies Funding Source Rodents In Vivo Studies In Vitro Studies Lipids Blood RNA Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Fluorescent Antibody Technique Cell Viability Descriptive Statistics Data Analysis Software One-Way Analysis of Variance Post Hoc Analysis ab: Background: Niemann-Pick C1-like 1 (NPC1L1) mediates cholesterol absorption and plays major roles in cholesterol homeostasis. Our previous study showed that curcumin reduced NPC1L1 expression and cholesterol absorption in Caco-2 cells. This study aimed to investigate whether curcumin could prevent hypercholesterolemia by transcriptionally suppressing intestinal and hepatic NPC1L1 expression via inhibition of sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) transcriptional activity. Methods: Male hamsters were fed a high-fat diet (HFD) with or without 0.1% w/w curcumin for 12 weeks. Additionally, Caco-2 cells and HepG2 cells were treated with 6, 12, 25, or 50 µmol/L curcumin for 24 h. The cholesterol absorption was determined with 22-NBD-cholesterol assay, the promoter activity of NPC1L1 and the transcriptional activity of SREBP-2 and HNF1α were determined with luciferase assay, and the gene expression of NPC1L1, SREBP-2, and HNF1α and the nuclear abundance of SREBP-2 and HNF1α were measured by RT-qPCR and Western blotting, respectively. Results: Compared to HFD-fed hamsters, curcumin supplementation significantly lowered cholesterol levels in the serum (20.2%,) and liver (26.1%), and increased fecal neutral sterol excretion (114.5%). In addition, curcumin significantly reduced the gene expression of NPC1L1, SREBP-2, and HNF1α and the nuclear abundance of SREBP-2 and HNF1α in the small intestine and liver of HFD-fed hamsters. Furthermore, the dual luciferase assay showed that the promoter activity of NPC1L1 and the transcriptional activity of SREBP-2 and HNF1α in Caco-2 and HepG2 cells were dose-dependently inhibited after 24 h curcumin treatment, and maximally inhibited by 50 µmol/L curcumin. Additionally, the gene expression of NPC1L1, SREBP-2, and HNF1α and the nuclear abundance of SREBP-2 and HNF1α in Caco-2 and HepG2 cells were consistently suppressed by curcumin. Curcumin also significantly reduced the cholesterol uptake in both Caco-2 and HepG2 cells. Conclusions: Our findings indicate that curcumin prevents HFD-induced hypercholesterolemia by transcriptionally suppressing intestinal and hepatic NPC1L1 expression and cholesterol absorption via inhibition of SREBP-2 and HNF1α transcriptional activity. Our research provides evidence for curcumin as a potential nutraceutical for hypercholesterolemia treatment by regulating NPC1L1 and enterohepatic circulation metabolism of cholesterol. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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