Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1–AMPK signaling pathway in mice |
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| Institution: | 1. Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China;2. Zhongshan Medical College of Sun Yat-sen University, Guangzhou 510080, China;3. Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China;4. Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China;1. State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu 611137, China;2. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;1. Department of General Surgery, Istanbul Medeniyet University, School of Medicine, Istanbul, Turkey;2. Department of Biochemistry, Istanbul Medeniyet University, School of Medicine, Istanbul, Turkey;1. Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences (TUMS), Tehran, Iran;2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ethiopia;4. Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;5. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;6. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Internal Medicine III, University Hospital, RWTH Aachen, Aachen, Germany;2. Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States;3. Institute of Translational Immunology and Research Center for Immunotherapy, University Medical Center, Mainz, Germany;4. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;5. Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK |
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| Abstract: | The current study was conducted to investigate the anti-fibrotic effect and its possible underlying mechanisms of thymoquinone (TQ) against hepatic fibrosis in vivo. TQ is the major active compound derived from the medicinal Nigella sativa. Liver fibrosis was induced in male Kunming mice by intraperitoneal injections of thioacetamide (TAA, 200 mg/kg). Mice were treated concurrently with TAA alone or TAA plus TQ (20 mg/kg or 40 mg/kg) given daily by oral gavage. Our data demonstrated that TQ treatment obviously reversed liver tissue damage compared with TAA alone group, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM) proteins. TQ significantly attenuated TAA-induced liver fibrosis, accompanied by reduced protein and mRNA expression of α-smooth muscle actin (α-SMA), collagen-? and tissue inhibitor of metalloproteinase-1 (TIMP-1). TQ downregulated the expression of toll-like receptor 4 (TLR4) and remarkably decreased proinflammatory cytokine levels as well. TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K) phosphorylation. Furthermore, TQ enhanced the phosphorylation adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B (LKB)-1. In conclusion, TQ may reduce ECM accumulation, and it may be at least regulated by phosphorylation of AMPK signaling pathways, suggesting that TQ may be a potential candidate for the therapy of hepatic fibrosis. |
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