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Inflammation

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

  • Ayman M. MahmoudEmail author
  • Walaa G. Hozayen
  • Iman H. Hasan
  • Eman Shaban
  • May Bin-Jumah
ORIGINAL ARTICLE
  • 13 Downloads

Abstract

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 of UMB against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats received CCl4 and UMB for 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.

KEY WORDS

fibrosis 7-hydroxycoumarin oxidative stress inflammation TGF-β1 PPARγ 

Notes

Authors’ Contribution

AMM, WGH, and IHH conceived the study and designed the experiments. AMM and ES performed the experiments. AMM analyzed the data, prepared the figures, and wrote the manuscript. All the authors participated in the assays, revised the manuscript, and approved the submission.

Compliance with Ethical Standards

The experimental protocol and all animal procedures were approved by the Institutional Animal Ethics Committee of Beni-Suef University (Egypt).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Physiology Division, Zoology Department, Faculty of ScienceBeni-Suef UniversityBeni-SuefEgypt
  2. 2.Biochemistry Division, Chemistry Department, Faculty of ScienceBeni-Suef UniversityBeni-SuefEgypt
  3. 3.Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS)Beni-Suef UniversityBeni-SuefEgypt
  4. 4.Department of Pharmacology and Toxicology, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Department of Biology, College of SciencePrincess Nourah bint Abdulrahman UniversityRiyadhSaudi Arabia

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