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Naringin inhibits matrix metalloproteinase‐9 expression and AKT phosphorylation in tumor necrosis factor‐α‐induced vascular smooth muscle cells
Author(s) -
Lee EoJin,
Kim DongIl,
Kim WunJae,
Moon SungKwon
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800210
Subject(s) - naringin , phosphorylation , tumor necrosis factor alpha , matrix metalloproteinase , protein kinase b , tumor necrosis factor α , microbiology and biotechnology , chemistry , cancer research , matrix (chemical analysis) , vascular smooth muscle , smooth muscle , biology , endocrinology , biochemistry , chromatography
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‐α (TNF‐α)‐induced expression of MMP‐9, under 10–25 μM concentration conditions in vascular smooth muscle cells (VSMC). The TNF‐α‐induced invasion and migration of VSMC were inhibited by naringin. Furthermore, naringin suppressed TNF‐α‐mediated release of interleukin‐6 and ‐8 (IL‐6 and IL‐8). However, naringin (10–25 μM) treatment of VSMC in the presence of TNF‐α did not affect cell growth and apoptosis. In additional experiments, naringin reduced the transcriptional activity of activator protein‐1 and nuclear factor kappaB (NF‐κB), 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‐α‐induced VSMC. Treatment of aglycone naringenin (10–25 μM) had same effect on the levels of MMP‐9 expression, invasion, migration, and AKT phosphorylation in TNF‐α‐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‐κB and activator protein‐1 in TNF‐α‐induced VSMC. These novel findings provide a theoretical basis for the preventive use of naringin for atherosclerosis disease.