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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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