Umbelliferone Ameliorates CCl4-Induced Liver Fibrosis in Rats by Upregulating PPARγ and Attenuating Oxidative Stress, Inflammation, and TGF-β1/Smad3 Signaling

Journal Article
Bin-Jumahn,, Ayman M. Mahmoud , Walaa G. Hozayen, Iman H. Hasan, Eman Shaba, May . 2019
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مستخلص المنشور: 

Umbelliferone (UMB) is a natural coumarin that has diverse biological activities.

However, its potential to protect against liver fibrosis has not been reported yet. This study

aimed to investigate the protective effect ofUMB against carbon tetrachloride (CCl4)-induced

liver fibrosis in rats. Rats received CCl4 and UMBfor 8 weeks and samples were collected for

analyses. CCl4 induced a significant increase in serum levels of liver function markers and

pro-inflammatory cytokines. Treatment with UMB significantly ameliorated liver function

markers and pro-inflammatory cytokines and prevented CCl4-induced histological alterations.

CCl4 promoted significant upregulation of α-smooth muscle actin (SMA), collagen I,

collagen III, NF-κB p65, TGF-β1, and p-Smad3. Masson’s trichrome staining revealed a

significant fibrogenesis in CCl4-induced rats. Treatment with UMB suppressed TGF-β1/

Smad3 signaling and downregulated α-SMA, collagen I, collagen III, and NF-κB p65. In

addition, UMB diminished malondialdehyde and nitric oxide levels, boosted reduced glutathione

and antioxidant enzymes, and upregulated the expression of PPARγ. In conclusion,

our results demonstrated that UMB prevented CCl4-induced liver fibrosis by attenuating

oxidative stress, inflammation, and TGF-β1/Smad3 signaling, and upregulating PPARγ.

Therefore, UMB may be a promising candidate for preventing hepatic fibrogenesis, given

that further research is needed to delineate the exact molecular mechanisms underlying its

antifibrotic efficacy.

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