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Hepatoprotective effects of flexirubin, a novel pigment from Chryseobacterium artocarpi, against carbon tetrachloride-induced liver injury: An in vivo study and molecular modeling.

Authors
  • Mogadem, Abeer1
  • Naqvi, Arshi2
  • Almamary, Mohamed Ali2
  • Ahmad, Wan Azlina3
  • Jemon, Khairunadwa4
  • El-Alfy, Sherif Helmy5
  • 1 Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru, Malaysia; Department of Chemistry, College of Science, Taibah University, Almadinah Almunawarah, Saudi Arabia. , (Malaysia)
  • 2 Department of Chemistry, College of Science, Taibah University, Almadinah Almunawarah, Saudi Arabia. , (Saudi Arabia)
  • 3 Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru, Malaysia. Electronic address: [email protected] , (Malaysia)
  • 4 Department of Bioscience, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru, Malaysia. , (Malaysia)
  • 5 Department of Zoology, Faculty of Science, Ain Shams University, Cairo, Egypt; Department of Biology, College of Science, Taibah University, Almadinah Almunawarah, Saudi Arabia. Electronic address: [email protected] , (Egypt)
Type
Published Article
Journal
Toxicology and Applied Pharmacology
Publisher
Elsevier
Publication Date
Apr 15, 2022
Volume
444
Pages
116022–116022
Identifiers
DOI: 10.1016/j.taap.2022.116022
PMID: 35436475
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Liver injuries caused by various industrial chemicals represent a serious health concern worldwide. Flexirubins are a novel class of naturally occurring bacterial pigments whose bioactivity remains largely unexplored. The present study evaluated the hepatoprotective effects of flexirubin pigment extracted from the bacterium Chryseobacterium artocarpi against CCl4-induced acute liver injury in mice. Flexirubin was applied at three different oral doses, 125, 250 and 500 mg/kg bw/d for seven consecutive days. Treatment of animals with flexirubin before exposure to CCl4 (10 mL/kg bw dissolved in olive oil, 1:1 v/v) significantly decreased the elevated serum levels of ALT, AST, ALP, LDH and TBL. Flexirubin pretreatment showed a great capability for attenuating the CCl4-induced oxidative stress by decreasing the level of liver MDA, and increasing the antioxidant enzyme activities of liver SOD and CAT, and the levels of GSH and TAC. Flexirubin also alleviated the histopathological alterations in liver by prohibiting steatosis, ballooning degeneration, leukocytic infiltration and necrosis. Immunohistochemical analysis demonstrated that flexirubin has a significant anti-apoptotic activity against CCl4 via upregulation of Bcl-2, and downregulation of Bax, Caspase-3 and TGF-β1. Flexirubin also exhibited a remarkable anti-inflammatory activity against CCl4 through its suppressive action on TNF-α, COX-2 and CD-45. Flexirubin could trigger upregulation of the Nrf2/HO-1 signaling pathway mediating protection against CCl4. In silico molecular docking revealed flexirubin as a potential inhibitor against two target proteins, TGF-β1 and TACE. The results proved the effectiveness of flexirubin as a significant source of natural compounds for its use in drug formulation strategies to offer protection against hepatotoxins. Copyright © 2022. Published by Elsevier Inc.

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