Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-alpha-induced vascular smooth muscle cells

作者：Lee Eo Jin; Kim Dong Il; Kim Wun Jae; Moon Sung Kwon^*

来源：Molecular Nutrition & Food Research, 2009, 53(12): 1582-1591.

DOI：10.1002/mnfr.200800210

• MMP-9
• Naringin
• PI3K/AKT/mTOR/p70S6K pathway
• TNF-alpha
• Vascular smooth muscle cell

Citrus fruits are high in naringin, which has a beneficial effect on cardiovascular diseases. However, the matrix metalloproteinase-9 (MMP-9) regulation involved in cell migration and invasion remains to be identified. Naringin inhibited tumor necrosis factor-alpha (TNF-alpha)induced expression of MMP-9, under 10-25 mu M concentration conditions in vascular smooth muscle cells (VSMC). The TNF-alpha-induced invasion and migration of VSMC were inhibited by naringin. Furthermore, naringin suppressed TNF-alpha-mediated release of interleukin-6 and -8 (IL-6 and IL-8). However, naringin (10-25 mu M) treatment of VSMC in the presence of TNF-alpha did not affect cell growth and apoptosis. In additional experiments, naringin reduced the transcriptional activity of activator protein-1 and nuclear factor kappaB (NF-kappa B), which are two important nuclear transcription factors that;are involved in MMP-9 expression. Also, naringin treatment blocked PI3K/AKT/mTOR/p70S6K pathway in TNF-alpha-induced VSMC. Treatment of aglycone naringenin (10-25 mu M) had same effect on the levels of MMP-9 expression, invasion, migration, and AKT phosphorylation in TNF-alpha-induced VSMC, compared with naringin treatment. These results suggest that naringin represses PI3K/AKT/mTOR/p70S6K pathway, invasion and migration, and subsequently suppresses MMP-9 expression through the transcription factors NF-kappa B and activator protein-1 in TNF-alpha-induced VSMC. These novel findings provide a theoretical basis for the preventive use of naringin for atherosclerosis disease.

• 出版日期2009-12