Rosmarinic acid stimulates liver regeneration through the mTOR pathway

Phytomedicine. 2016 Dec 1;23(13):1574-1582. doi: 10.1016/j.phymed.2016.09.010. Epub 2016 Sep 30.

Abstract

Background: Rosemary (Rosmarinus offcinsalis L) has a liver protection function under various conditions of liver damage. Rosmarinic acid, one of the pharmacological constituents of rosemary, exhibited protective effects against organ injury, including acute liver injury.

Hypothesis: We hypothesize that RA stimulates liver regeneration.

Study design: In the present study, we investigated the effects and mechanism of RA administration on liver regeneration using partial hepatectomy (PH), a well-validated liver regeneration model in mice.

Methods: We use a 2/3 partial hepatectomy (PH) model to induce liver regeneration. RA was administered prior to and simultaneously with PH. The regeneration process was estimated by the index of the liver to body weight (ILBW) and the expression of proliferating cell nuclear antigen (PCNA) and liver transaminases.

Results: The administration of rosmarinic acid stimulated hepatocyte proliferation based on activation of the mTOR/S6K pathway. Rosmarinic acid treatment also rescued impaired liver function due to PH.

Conclusion: These data demonstrate that RA is potentially useful to promote liver regeneration.

Keywords: Liver regeneration; Partial hepatectomy; Proliferation; Rosemary; Rosmarinic acid; mTOR.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Proliferation / drug effects
  • Cinnamates / pharmacology*
  • Depsides / pharmacology*
  • Hepatectomy
  • Hepatocytes / drug effects
  • Liver / drug effects*
  • Liver / physiopathology
  • Liver / surgery
  • Liver Function Tests
  • Liver Regeneration / drug effects*
  • Male
  • Mice, Inbred C57BL
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rosmarinic Acid
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Cinnamates
  • Depsides
  • Proliferating Cell Nuclear Antigen
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases