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

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.