Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling

Phytomedicine. 2016 Jan 15;23(1):58-67. doi: 10.1016/j.phymed.2015.12.004. Epub 2015 Dec 21.

Abstract

Background: Cryptotanshinone (CT), a major tanshinone found in Salvia miltiorrhiza Bunge (Lamiaceae), has various pharmacological effects such as antitumor, anti-inflammatory, and antioxidant properties. Despite its well-documented benefits in a wide range of diseases, the effect of CT on adipocyte differentiation has not been well characterized.

Purpose: The present study was designed to determine the in vitro anti-adipogenic effect and underlying molecular mechanisms of CT using 3T3-L1 murine pre-adipocytes.

Methods: We measured the levels of intracellular triglyceride accumulation and mRNA and protein expression of key adipogenic transcription factors and their target genes.

Results: Treatment with CT drastically reduced lipid accumulation in a dose- and time-dependent manner. Molecular assays showed that CT effectively suppressed the expression of C/EBPβ, C/EBPα, and PPARγ and of their target adipocyte-specific genes aP2, adiponectin, and GLUT4 but activated the expression of anti-adipogenic genes such as GATA2, CHOP10, and TNF-α. CT treatment also inhibited the phosphorylation of STAT3 in the early phase of adipogenesis. A small-interfering-RNA-mediated knock-down of STAT3 potentiated the anti-adipogenic effect of CT.

Conclusion: Taken together, the results suggest that CT may be a good anti-adipogenic candidate because it regulates STAT3 during early adipogenesis.

Keywords: Adipogenesis; C/EBPβ; Cryptotanshinone; PPARγ; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects*
  • Adiponectin / metabolism
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Differentiation / drug effects
  • Gene Expression Regulation
  • Gene Silencing
  • Glucose Transporter Type 4 / metabolism
  • Mice
  • PPAR gamma / metabolism
  • Phenanthrenes / pharmacology*
  • Phosphorylation
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Salvia miltiorrhiza / chemistry
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adiponectin
  • Adipoq protein, mouse
  • CCAAT-Enhancer-Binding Protein-alpha
  • CCAAT-Enhancer-Binding Protein-beta
  • Glucose Transporter Type 4
  • PPAR gamma
  • Phenanthrenes
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Slc2a4 protein, mouse
  • Stat3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • cryptotanshinone