title: Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators.
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.
authors.affiliation: Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
authors.forename: Mardi M
authors.initials: MM
authors.lastname: Algandaby
authors.affiliation: Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-Halawany
authors.affiliation: Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Abdallah
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Alahdal
authors.affiliation: Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Ayman A
authors.initials: AA
authors.lastname: Nagy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, P.O. Box 80260, 21589, Saudi Arabia.
authors.forename: Osama M
authors.initials: OM
authors.lastname: Ashour
authors.affiliation: Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. aaabdulalrahman1@kau.edu.sa.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, P.O. Box 80260, 21589, Saudi Arabia. aaabdulalrahman1@kau.edu.sa.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D002396:Catechols / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D005233:Fatty Alcohols / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D002396:Catechols; D005233:Fatty Alcohols; D018836:Inflammation Mediators; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C007845:gingerol; D002251:Carbon Tetrachloride
keywords: Gingerol; Hepatic fibrosis; Nuclear factor κB; Toll-like receptor 4
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