Umbelliferone Ameliorates CCl4-Induced Liver Fibrosis in Rats by Upregulating PPARγ and Attenuating Oxidative Stress, Inflammation, and TGF-β1/Smad3 Signaling
Bin-Jumahn,, Ayman M. Mahmoud , Walaa G. Hozayen, Iman H. Hasan, Eman Shaba, May . 2019
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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