The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125FAK-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2010 Jan 1|
Bibliographical noteFunding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant ( R11-2001-090-00000-0 ), the Korea Research Foundation Grand founded by the Korea government (MEST) (Regional Research Universities Program/Medical & Bio-Materials Research Center), the Research Grant ( PF0320701-00 ) from the Plant Diversity Research Center of 21st Frontier Research Program funded by the Korean Ministry of Science and Technology , and the Research Grant from the Korea Research Foundation ( KRF-2006-312-C00677 ).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology