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


OBJECTIVE
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).


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 β (PDGF-Rβ), extracellular signal regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB), or phospholipase C-γ1 (PLCγ1) was investigated by immunoblotting. Moreover, the effect of (2S)-naringenin on DNA synthesis and the cell cycle was examined using a [(3)H]-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-Rβ, Akt/PKB, ERK1/2, or PLCγ1. 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.
Department of Pharmacology, Chungnam National University College of Pharmacy, Yuseong-gu, Daejeon, Republic of Korea.
Jung-Jin
JJ
Lee
Hyoseok
H
Yi
In-Su
IS
Kim
Yohan
Y
Kim
Nguyen Xuan
NX
Nhiem
Young Ho
YH
Kim
Chang-Seon
CS
Myung
D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D032401:Typhaceae / Q000737:chemistry*
D016213:Cyclins; D044950:Flavanones; D010936:Plant Extracts; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor; D018844:Cyclin-Dependent Kinases; C005273:naringenin