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Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2016 Jun 30; Vol. 17 (7). Date of Electronic Publication: 2016 Jun 30. - Publication Year :
- 2016
-
Abstract
- Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-κB (NF-κB) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor β 1 (TGF-β1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation.
- Subjects :
- Actins metabolism
Animals
Apoptosis drug effects
Berberine pharmacology
Cell Line
Collagen genetics
Collagen metabolism
Disease Models, Animal
Hepatic Stellate Cells cytology
Hepatic Stellate Cells drug effects
Hepatic Stellate Cells metabolism
Liver Cirrhosis chemically induced
Liver Cirrhosis metabolism
Liver Cirrhosis pathology
Male
Matrix Metalloproteinases genetics
Matrix Metalloproteinases metabolism
Mice
Mice, Inbred ICR
Rats
Smad Proteins metabolism
Thioacetamide toxicity
Tissue Inhibitor of Metalloproteinases genetics
Tissue Inhibitor of Metalloproteinases metabolism
Transforming Growth Factor beta1 metabolism
Berberine analogs & derivatives
NF-kappa B metabolism
Protective Agents pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 27376272
- Full Text :
- https://doi.org/10.3390/ijms17071036