Genistein, Daidzein and Glycitein Inhibit Growth and DNA Synthesis of Aortic Smooth Muscle Cells from Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB-induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.

Database of traditional Chinese medicine and its application to studies of mechanism and to prescription validation

“…Angiogenesis (Pan et al, 2001) 1aa9 C-HA-RAS Genistein blocks RAS activation (Takahashi et al, 1997).…”

Isoflavone Attenuates Vascular Contraction through Inhibition of the RhoA/Rho-Kinase Signaling Pathway

“…The soybean isoflavones, genistein, daidzein, and glycitein, may have potential benefits in regards to human health maintenance because of their biological effects (Pan et al, 2001). Isoflavones (phytoestrogens) have gained considerable attention for their potential role in improving risk factors regarding cardiovascular diseases (Sacks et al, 2006).…”

“…Soy protein containing isoflavones has been observed to have several beneficial effects on cardiovascular health; a meta-analysis study showed that total cholesterol decreased by 9.3%, triglyceride by 10.5%, and low-density lipoprotein cholesterol by 12.9%, when an average of 47 g of soy protein was consumed daily (Anderson et al, 1995). Soybean isoflavones were suggested to inhibit proliferation of vascular smooth muscle and thus contribute to the prevention of atherosclerotic cardiovascular diseases (Pan et al, 2001).…”

Phytoestrogens

“…Effects of isoflavones on cardiovascular health 240 DIXON may result from inhibition of low-density lipoprotein (LDL) oxidation (178,179), an effect that may be enhanced by food sources rich in vitamim C (82); inhibition of proliferation of aortic smooth muscle cells, as concluded from a study with strokeprone spontaneously hypertensive rats (148); and maintenance of the physical properties of arterial walls (185).…”