Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice.

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-І 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.

• Authors: Ting Bai, Yong Yang, Yan-Ling Wu, Shuang Jiang, Jung Joon Lee, Li-Hua Lian, Ji-Xing Nan
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 19 Issue 2 Pg. 351-7 (Apr 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24560906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Acta2 protein, mouse
• Actins
• Anti-Inflammatory Agents
• Benzoquinones
• Collagen Type I
• Cytokines
• Timp1 protein, mouse
• Tissue Inhibitor of Metalloproteinase-1
• Thioacetamide
• Protein Serine-Threonine Kinases
• Stk11 protein, mouse
• AMP-Activated Protein Kinases
• thymoquinone

Topics

• AMP-Activated Protein Kinases (metabolism)
• Actins (genetics, metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Benzoquinones (pharmacology, therapeutic use)
• Collagen Type I (genetics, metabolism)
• Cytokines (genetics)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis (chemically induced, drug therapy, metabolism, pathology)
• Male
• Mice
• Protein Serine-Threonine Kinases (metabolism)
• Signal Transduction (drug effects)
• Thioacetamide
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)