Research Article Details
| Article ID: | A49063 |
| PMID: | 19594758 |
| Source: | Br J Pharmacol |
| Title: | Curcumin suppresses expression of low-density lipoprotein (LDL) receptor, leading to the inhibition of LDL-induced activation of hepatic stellate cells. |
| Abstract: | BACKGROUND AND PURPOSE: Obesity is often accompanied by hypercholesterolemia characterized by elevated levels of plasma low-density lipoprotein (LDL) and associated with non-alcoholic steatohepatitis, which could progress to hepatic fibrosis. Hepatic stellate cells (HSCs) are the major effectors of hepatic fibrogenesis. This study aims to clarify effects of LDL on activation of HSC, to evaluate roles of curcumin in suppressing these effects and to further elucidate the underlying molecular mechanisms. EXPERIMENTAL APPROACHES: HSCs were prepared from rats and cell proliferation was measured by cell proliferation assays (MTS assays). Transient transfection assays were performed to evaluate gene promoter activities. Real-time polymerase chain reaction and Western blotting were used to analyse the expression of genes. KEY RESULTS: LDL stimulated HSC activation in vitro, which was attenuated by curcumin. Curcumin reduced the abundance of LDL receptor (LDLR) in activated HSCs, decreasing cellular cholesterol. Curcumin-dependent activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) differentially regulated the expression of the transcription factors, sterol regulatory element-binding proteins (SREBPs), in activated HSCs, resulting in the suppression of LDLR gene expression. CONCLUSIONS AND IMPLICATIONS: Curcumin suppressed LDLR gene expression in activated HSCs in vitro by activating PPARgamma and differentially regulating gene expression of SREBPs, reducing cellular cholesterol and attenuating the stimulatory effects of LDL on HSC activation. These results provide novel insights into the roles and mechanisms of curcumin in the inhibition of LDL-induced HSC activation. This curcumin, a constituent of turmeric, may be useful in preventing hypercholesterolemia-associated hepatic fibrogenesis. |
| DOI: | 10.1111/j.1476-5381.2009.00261.x |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D092 | Curcumin | Chemical drug | DB11672 | PPARG; COX inhibitor | Anticancer agent; NSAID | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |