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Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators

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Abstract

6-Gingerol (Gin) is known to possess hepatoprotective effects. Liver fibrosis is a major health concern that results in significant morbidity and mortality. There is no FDA-approved medication for liver fibrosis. The present work aimed at exploring the beneficial effects of Gin against liver fibrosis in rats. Experimental fibrosis was induced by challenging animals with CCl4 for 6 weeks. Gin significantly ameliorated the increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, albumin, total cholesterol (TC) and triglyceride (TG) concentrations, and liver index. These effects were confirmed by light and electron microscopic examinations. The antifibrotic effects were confirmed by examining Masson trichrome-stained liver sections which indicated reduced collagen deposition in Gin-treated animals. Further, Gin administration hampered alpha-smooth muscle actin (α-SMA) expression and significantly reduced hepatic content of transforming growth factor-beta (TGF-β). Also, Gin elicited profound antioxidant actions as indicated by preventing reduced glutathione (GSH) depletion and lipid peroxide accumulation. The observed antifibrotic activities involved decreased production of nuclear factor κB (NF-κB), tumor necrosis factor alpha (TNF-α), expression of toll-like receptor 4 (TLR4), intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM). Involvement of Gin anti-inflammatory activity was verified by the decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in livers of animals treated with Gin. Thus, it can be concluded that Gin protects against CCl4-induced liver fibrosis in rats. This can be ascribed, at least partly, to its antioxidant, anti-inflammatory effects as well as the inhibition of NF-κB/TLR-4 expression.

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Acknowledgments

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant no. 30/34/RG. The authors, therefore, acknowledge with thanks the DSR technical and financial support.

MA, AMA, AN, OA, and ABA participated in the biochemical and immunohistochemical studies. AN and MA performed the histopathological studies. AE and HA prepared, purified, and characterized 6-gingerol. AE, HA, and AN performed data analysis. All authors participated in writing the manuscript. OA and ABA prepared the manuscript for final submission.

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Authors and Affiliations

  1. Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Mardi M. Algandaby, Ali M. El-halawany, Hossam M. Abdallah & Ashraf B. Abdel-Naim

  2. Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Mardi M. Algandaby

  3. Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Ali M. El-halawany & Hossam M. Abdallah

  4. Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Abdulrahman M. Alahdal

  5. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Tanta, Egypt

    Ayman A. Nagy

  6. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, P.O. Box 80260, 21589, Saudi Arabia

    Osama M Ashour & Ashraf B. Abdel-Naim

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  1. Mardi M. Algandaby
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  2. Ali M. El-halawany
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  7. Ashraf B. Abdel-Naim
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Corresponding author

Correspondence to Ashraf B. Abdel-Naim.

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Animal handling and experimental protocol were approved by the Unit of Biomedical Ethics, Faculty of Medicine, King Abdulaziz University (Reference No. 157–14).

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The authors declare that they have no competing interests.

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Algandaby, M.M., El-halawany, A.M., Abdallah, H.M. et al. Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators. Naunyn-Schmiedeberg's Arch Pharmacol 389, 419–428 (2016). https://doi.org/10.1007/s00210-016-1210-1

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  • DOI: https://doi.org/10.1007/s00210-016-1210-1

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