Sophoridine Counteracts Obesity via Src-Mediated Inhibition of VEGFR Expression and PI3K/AKT Phosphorylation

Int J Mol Sci. 2024 Jan 19;25(2):1206. doi: 10.3390/ijms25021206.

Abstract

Sophoridine (SRP) is a natural quinolizidine alkaloid found in many traditional Chinese herbs, though its effect on adipose tissue is unclear. We improved serum lipid levels by administering SRP by gavage in high-fat diet (HFD)-fed C57BL/6 mice. After 11 weeks, SRP supplementation significantly reduced body weight gain and improved glucose homeostasis, while reducing subcutaneous fat and liver weight. SRP also inhibited cell proliferation and differentiation of 3T3-L1 cells. Proteomics analysis revealed that SRP inhibits adipocyte differentiation by interacting with Src, thereby suppressing vascular endothelial growth factor receptor 2 (VEGFR2) expression and PI3K/AKT phosphorylation. This study provides an empirical basis for the treatment of obesity with small molecules.

Keywords: PI3K/AKT; Src; VEGFR2; obesity; phosphorylation; sophoridine.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipogenesis
  • Animals
  • Diet, High-Fat / adverse effects
  • Matrines*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy
  • Obesity / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Matrines
  • Phosphatidylinositol 3-Kinases
  • Vascular Endothelial Growth Factor A