Research Article Details
| Article ID: | A26837 |
| PMID: | 19681867 |
| Source: | Br J Pharmacol |
| Title: | Curcumin adds spice to the debate: lipid metabolism in liver disease. |
| Abstract: | Activated hepatic stellate cells (HSCs), the major source of the collagens involved in fibrosis and non-alcoholic fatty liver disease (NAFLD), undergo a profound loss of lipid and vitamin A storage capacity, as a consequence of a decline in expression of 'adipogenic' transcription factors such as peroxisome proliferator-activated receptor-gamma (PPARgamma). By contrast, hepatocytes undergo a micro- and macro-vesicular steatosis, reflecting the accumulation of triacylglycerol, and associated with chronic inflammation and fibrosis. These paradoxical findings are extended in this issue: Kang and Chen demonstrate that while low-density lipoproteins (LDL) can activate HSCs, curcumin can inhibit this process by activation of PPARgamma, which not only represses gene expression of SREBP-2 and LDLR, but via induction of expression of SREBP-1c, restores the lipid storage capacity characteristic of quiescent HSCs, suggesting that curcumin may be of therapeutic usage in protecting against liver steatosis and fibrosis. |
| DOI: | 10.1111/j.1476-5381.2009.00335.x |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D092 | Curcumin | Chemical drug | DB11672 | PPARG; COX inhibitor | Anticancer agent; NSAID | Under clinical trials | Details |