New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans

PLoS One. 2017 Mar 3;12(3):e0172900. doi: 10.1371/journal.pone.0172900. eCollection 2017.

Abstract

Introduction: The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties.

Aims: This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model.

Results: The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages.

Conclusion: Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Curcumin / administration & dosage*
  • Diet, High-Fat
  • Disease Models, Animal
  • Fatty Liver / drug therapy
  • Fatty Liver / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Humans
  • Leptin / administration & dosage
  • Linoleic Acid / administration & dosage
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Leptin
  • Reactive Oxygen Species
  • Linoleic Acid
  • Curcumin

Grants and funding

ACCH received the following fundings: Grant CM05 from the University of Buenos Aires, PIP0051 from the National Council for Scientific and Technological Investigation, PICT 2012-2598 from the National Agency for the Promotion of Technology and Science.