Trillin Reduces Liver Chronic Inflammation and Fibrosis in Carbon Tetrachloride (CCl4) Induced Liver Injury in Mice

Immunol Invest. 2016 Jul;45(5):371-82. doi: 10.3109/08820139.2015.1137935. Epub 2016 May 24.

Abstract

Trillin is an active ingredient isolated from Dioscorea nipponica Makino. This study investigated the anti-inflammatory and anti-fibrosis effects of trillin on CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation and fibrosis were induced by intraperitoneal administration of CCl4 0.5 μL/g of body weight twice a week for 6 weeks. Trillin (50 mg/kg, 100 mg/kg) was administered by gavage for 12 days before finishing the CCl4 induction. Aspartate amino-transferase (AST) and glutamic-pyruvic transaminase (ALT) in serum were determined by AST and ALT kits. Superoxidase dismutase (SOD) activity and malondialdehyde (MDA) levels in serum were assayed by SOD and MDA kits. Meanwhile, the levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay (ELISA) method. Pathological changes were observed by hematoxylin-eosin (HE) staining. The proteins of the NF-κB pathway and the TGF-β/Smad pathway were measured by western blot. The trillin-treated group exhibited reduced AST, ALT, MDA, IL-6, TNF-α, and IL-1β, and increased SOD. Histological analyses of the trillin-treated group exhibited reduced inflammatory process and prevented liver fibrosis. Western blot analyses of the trillin-treated group showed reduced NF-κB pathway and TGF-β/Smad pathway.

Significance: Based on the results of the present study, trillin can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

Keywords: Liver fibrosis; NF-κB; TGF-β/Smad; liver inflammation; trillin.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Carbon Tetrachloride / administration & dosage
  • Carbon Tetrachloride / toxicity
  • Dioscorea / chemistry*
  • Enzyme-Linked Immunosorbent Assay
  • Hepatitis / blood
  • Hepatitis / drug therapy*
  • Hepatitis / pathology
  • Humans
  • Injections, Intraperitoneal
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • Male
  • Malondialdehyde / blood
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / blood
  • Saponins / therapeutic use*
  • Superoxide Dismutase / blood
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Saponins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Malondialdehyde
  • Carbon Tetrachloride
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase