ReferenceID 1699
Curcumol may reverse early and advanced liver fibrogenesis through downregulating the uPA/uPAR pathway
Phytother Res
Previous studies have suggested strong antifibrotic activity of curcumol in the liver; the underlying mechanisms of which, however, remain largely unknown. Aiming to investigate the role of curcumol in regulating early a
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- Reference Id
- 1699
- Evidence Id
- 18289
- Core Evidence Id
- 18289
- Source Reference Id
- 3389
- Herb2 Reference Id
- HBREF004186
- Subject Paper Key
- HBIN021990_31989700
- Pubmed Id
- 31989700
- Doi
- 10.1002/ptr.6616
- Paper Title
- Curcumol may reverse early and advanced liver fibrogenesis through downregulating the uPA/uPAR pathway
- Paper Abstract
- Previous studies have suggested strong antifibrotic activity of curcumol in the liver; the underlying mechanisms of which, however, remain largely unknown. Aiming to investigate the role of curcumol in regulating early and advanced liver fibrosis, we designed a rat model with advanced liver fibrosis and cell model with an initial fibrotic stage. Model rats induced by CCl4 and alcohol presented advanced liver fibrosis with complete fibrous septa. The administration of curcumol (25 mg/kg or 50 mg/kg) resulted in reversal of liver fibrosis. Leptin-administrated liver sinusoidal endothelial cells presented defenestration and basement membrane components deposition, including laminin (LN) and type IV collagen (Col IV), the characteristics of capillarization by scanning electron microscopy and immunofluorescence assays. After treatment with curcumol (12.5, 25, or 50 mg/L), defenestration was restored and the levels of LN and Col IV were decreased, consistent with the rat model. Quantitative polymerase chain reaction and Western blot results revealed that increased levels of urokinase plasminogen activator (uPA)/ uPA receptor (uPAR) were observed both in vivo and in vitro, curcumol significantly reduced uPA/uPAR at both the mRNA and protein levels. Reduction of uPA/uPAR may be synergistic with matrix metallopeptidase 13 to reverse liver fibrogenesis. In conclusion, curcumol protects liver from phenotypic changes in the early and advanced fibrogenesis, possibly through uPA/uPAR pathway.
- Journal
- Phytother Res
- Publish Year
- 2020
- Experiment Subject
- rat; leptin-administrated liver sinusoidal endothelial cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Advanced Liver Fibrosis; Complete Fibrous Septa; Liver Fibrosis
- Paper Title Cn
- Paper Title En
- Curcumol may reverse early and advanced liver fibrogenesis through downregulating the uPA/uPAR pathway
- Bilingual Status
- semi_complete