(2S)-Naringenin from Typha angustata inhibits vascular smooth muscle cell proliferation via a G0/G1 arrest

Ethnopharmacological relevance: Typha angustata is used in traditional Chinese medicine for a variety of clinical disorders. Its pharmacological actions include beneficial effects on hyperlipidemia and myocardial infarction, as well as labor-inducing and antibacterial effects. Aim of the study: We investigated the mechanism underlying the ability of (2S)-naringenin, an active compound from Typha angustata, to inhibit the proliferation of vascular smooth muscle cells (VSMCs). Materials and methods: After measuring the antiproliferative effect of (2S)-naringenin on VSMC proliferation using cell proliferation and viability assays, the possible involvement of a signaling pathway associated with platelet-derived growth factor receptor beta (PDGF-R beta), extracellular signal regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB), or phospholipase C-gamma 1 (PLC gamma 1) was investigated by immunoblotting. Moreover, the effect of (2S)-naringenin on DNA synthesis and the cell cycle was examined using a [H-3]-thymidine incorporation assay and flow cytometry. Results: (2S)-Naringenin significantly inhibited PDGF-BB-induced VSMC proliferation in a concentration-dependent manner, but did not affect signaling pathways associated with PDGF-R beta, Akt/PKB, ERK1/2, or PLC-gamma 1. However, (2S)-naringenin suppressed DNA synthesis via a G(0)/G(1) cell cycle arrest. Accordingly, the expression of cyclins D1 and E and cyclin-dependent kinases 2 and 4 was inhibited in a concentration-dependent manner; moreover, the phosphorylation of retinoblastoma protein was suppressed. Conclusions: Our results show that (2S)-naringenin inhibited the PDGF-BB-induced proliferation of VSMCs via a G(0)/G(1) arrest; thus, (2S)-naringenin may be valuable as a therapeutic agent for managing atherosclerosis and/or vascular restenosis. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.