Journal Article Beneficial Effect of 4-Methylumbelliferone Against Bile Duct Ligation-Induced Hepatic Fibrosis in Rats

Sawada, Naoya  ,  Mikami, Kenichiro  ,  Igarashi, Go  ,  Endo, Tetsu  ,  Sato, Ken  ,  Kakizaki, Ikuko  ,  Fukuda, Shinsaku

66 ( 2-4 )  , pp.143 - 151 , 2016-03-25 , 弘前大学大学院医学研究科・弘前医学会
Background & Aims: Liver fibrosis progresses to cirrhosis as the consequence of chronic liver injury. 4-methylumbelliferone (4-MU), a derivative of coumarin, has been used as an approved drug to treat biliary spasm. Recent publications have reported that 4-MU inhibits production of hyaluronan (HA), which is a key component of extracellular matrix deposition in fibrotic and cirrhotic liver. We investigated the effect of 4-MU on fibrotic liver in rats. Methods: Liver fibrosis was induced by bile duct ligation( BDL). Male Sprague-Dawley rats received a standard diet or the same diet containing 1% or 5% of 4-MU from 1 week before BDL. The rats were sacrificed at 3 weeks after BDL. Results: Administration of 4-MU increased serum 4-MU concentration levels, thereby decreasing serum HA levels in a dose-dependent manner. 4-MU treatment suppressed liver fibrosis in interlobular and pericentral areas with reduced alpha-smooth muscle actin expression, which suggested hepatic stellate cell activation.Conclusion: Treatment with 4-MU suppressed the experimental hepatic fibrosis accompanied by inhibition of HA production. Although further experimental studies are needed, 4-MU could protect against fibrogenesis and may be repurposed as a safe therapeutic application for hepatic fibrosis.

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