coumestrol and ipriflavone

Recently, dietary phytoestrogens (PEs) have been suggested as possible alternatives to estrogen therapy, as a means of preventing bone loss associated with ovarian hormone deficiency. PEs are non-steroidal, plant-derived compounds that exhibit some estrogen-like activity in some tissues, and which appear to prevent postmenopausal bone loss. While PEs act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption.. Therefore, the aim of this study was to investigate the effect of two dietary PEs (coumestrol and apigenin) as well as a synthetic PE, ipriflavone, on Ca absorption in human Caco-2 intestinal-like cells.. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On d 21, the Caco-2 monolayers (n 10-16 per treatment), grown in estrogen-free or low-estrogen media, were then exposed to 10 nM-1,25 (OH)2 D3, or 50 microM ipriflavone, -coumestrol or -apigenin for 48 hours. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured.. As expected, 1,25 (OH)2 D3 stimulated Ca absorption. Treatment with coumestrol or apigenin had no effect on Ca transport. On the other hand, ipriflavone increased total Ca transport (by about 1.5-fold, P < 0.05) under low-estrogen conditions, but not under estrogen-free conditions. This increase in total Ca transport by ipriflavone was via an increased transcellular Ca transport (by about 2-fold, P < 0.05) relative to control.. In conclusion, the protective effect of dietary PE on bone mass would appear to be due to their direct effect(s) on bone cells, as opposed to an indirect effect on bone by stimulation of intestinal Ca absorption.

Topics: Apigenin; Biological Transport; Bone and Bones; Caco-2 Cells; Calcium; Coumestrol; Humans; Intestinal Absorption; Isoflavones; Phytoestrogens

We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Bone Density; Bone Resorption; Calcification, Physiologic; Calcium; Calcium, Dietary; Chick Embryo; Coumestrol; Dinoprostone; Female; Femur; Interleukin-1; Isoflavones; Osteoporosis; Ovariectomy; Parathyroid Hormone; Rats; Rats, Wistar