Abstract | AIM: To investigate the effect of farrerol, a major active component isolated from a traditional Chinese herb "man-shan-hong" (the dried leaves of Rhododendron dauricum L) on fetal bovine serum (FBS)-induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rat thoracic aorta. METHODS: VSMCs proliferation, DNA synthesis and cell cycle progression were studied using the MTT assay, bromodeoxyuridine ( BrdU) incorporation and flow cytometry, respectively. The mRNA levels of cell cycle proteins were quantified using real-time RT-PCR, and the phosphorylation of ERK1/2 was determined using Western blotting. Reporter gene and receptor binding assays were employed to study the interaction between farrerol and estrogen receptors (ERs). RESULTS:
Farrerol (0.3-10 μmol/L) inhibited VSMC proliferation and DNA synthesis induced by 5% FBS in a concentration-dependent manner. The effects were associated with G(1) cell cycle arrest, down-regulation of cell cycle proteins and reduction in FBS-induced ERK1/2 phosphorylation. Using a reporter gene, it was found that farrerol (3 μmol/L) induced 2.1-fold transcription of ER. In receptor binding assays, farrerol inhibited the binding of [(3)H] estradiol for ERα and ERβ with IC(50) values of 57 μmol/L and 2.7 μmol/L, respectively, implying that farrerol had a higher affinity for ERβ. Finally, the inhibition of VSMC proliferation by farrerol (3 μmol/L) was abolished by the specific ERβ antagonist PHTPP (5 μmol/L). CONCLUSION:
Farrerol acts as a functional phytoestrogen to inhibit FBS-induced VSMC proliferation, mainly via interaction with ERβ, which may be helpful in the treatment of cardiovascular diseases related to abnormal VSMCs proliferation.
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Authors | Qun-yi Li, Li Chen, Yan-hui Zhu, Meng Zhang, Yi-ping Wang, Ming-wei Wang |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 32
Issue 4
Pg. 433-40
(Apr 2011)
ISSN: 1745-7254 [Electronic] United States |
PMID | 21399653
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromones
- DNA Primers
- Estrogen Receptor beta
- farrerol
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Topics |
- Animals
- Aorta, Thoracic
(cytology, drug effects)
- Base Sequence
- Blotting, Western
- Cell Proliferation
(drug effects)
- Chromones
(pharmacology)
- DNA Primers
- Estrogen Receptor beta
(physiology)
- Flow Cytometry
- Muscle, Smooth, Vascular
(cytology, drug effects)
- Polymerase Chain Reaction
- Rats
- Rats, Sprague-Dawley
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