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

Abstract

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 microM 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 microM) 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-kappaB), 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 microM) 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-kappaB 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.

<i>Citrus</i> Flavonoids and Human Cancers

“…Arivazhagan L et al [94] reported that tangeretin treatment significantly suppressed matrix metalloproteinase (MMP)-2, MMP-9 in a DMBA-induced animal models. Lee et al [107] found that naringin extracted from Citrus fruits including grapefruit suppressed the upregulation of MMP-9 and repressed the PI3K/AKT/mTOR signaling pathway. Naringenin were evaluated for its anti-metastasis effects by Lentini et al [108].…”

Naringin Protects against Kainic Acid-Induced Status Epilepticus in Rats: Evidence for an Antioxidant, Anti-inflammatory and Neuroprotective Intervention

“…This finding is supported by the study of Vanamala et al and other workers in which they have reported that naringin reduced the iNOS and COX-2 expression levels by inhibiting NF-kappa B activation. 53,60) In light of the above mentioned observations, it may be reasonable to assume that the potent antioxidant and anti-inflammatory effects of naringin contributes to its anti-convulsant activity.…”

Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-κB pathway

“…Naringin has recently received considerable attention as an antioxidant dietary supplement. Recently, growing evidence has indicated that naringin or naringenin displays antiinflammatory effects both in vitro and in vivo [15][16][17][18][19]. However, there is no information regarding the effects of naringin on ALI.…”