ReferenceID 43
Novel modulators of hepatosteatosis, inflammation and fibrogenesis
Hepatol Int
Alcoholic steatosis, instead of being innocuous, plays a critical role in liver inflammation and fibrogenesis. The severity of fatty liver is governed by the concerted balance between lipid transport, synthesis, and degr
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Record Fields
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- Reference Id
- 43
- Evidence Id
- 16633
- Core Evidence Id
- 16633
- Source Reference Id
- 82
- Herb2 Reference Id
- HBREF000223
- Subject Paper Key
- HBIN018163_26201319
- Pubmed Id
- 26201319
- Doi
- 10.1007/s12072-014-9526-8
- Paper Title
- Novel modulators of hepatosteatosis, inflammation and fibrogenesis
- Paper Abstract
- Alcoholic steatosis, instead of being innocuous, plays a critical role in liver inflammation and fibrogenesis. The severity of fatty liver is governed by the concerted balance between lipid transport, synthesis, and degradation. Whereas scavenger receptor class B, type I (SR-B1) is critical for reverse cholesterol uptake by the liver, peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1α and -β (PGC1α and PGC1β) are critical for lipid degradation and synthesis, respectively. Because betaine is a lipotropic agent, we have evaluated its effects on alcoholic steatosis. Betaine effectively prevented chronic alcohol-mediated (i) impaired SR-B1 glycosylation, plasma membrane localization, and consequent impaired cholesterol transport; and (ii) up regulation of PGC-1β, sterol regulatory element-binding protein 1c and downstream lipogenic genes with concomitant increased liver cholesterol, triglycerides and hepatic lipid score. Similarly, because of its anti-inflammatory and anti-fibrotic effects in other organs, we evaluated the protective effects of thymosin β4 (Tβ4) against carbon tetrachloride (CCl4)-induced hepatotoxicity in rat. Tβ4 prevented CCl4-induced (i) necrosis, inflammatory infiltration and up-regulation of α1(2)collagen, alpha-smooth muscle actin (α-SMA), platelet derived growth factor beta (PDGF-β) receptor and fibronectin mRNA expression; (ii) down-regulation of adipogenic gene, PPARγ and the up-regulation of epigenetic repressor gene, methyl CpG binding protein 2 (MeCP2) mRNA levels, suggesting that the anti-fibrogenic actions of Tβ4 involve the prevention of trans-differentiation of quiescent hepatic stellate cells into myo-fibroblasts largely by up-regulating PPARγ and by down-regulating MeCP2 genes. We therefore conclude that betaine and Tβ4 can effectively protect against alcoholic hepatosteatosis and hepatic fibrogenesis, respectively.
- Journal
- Hepatol Int
- Publish Year
- 2014
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Alcoholic Hepatosteatosis; Hepatic Fibrogenesis
- Paper Title Cn
- Paper Title En
- Novel modulators of hepatosteatosis, inflammation and fibrogenesis
- Bilingual Status
- semi_complete