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Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats.

ABSTRACT: Soy isoflavones and their metabolites, with estrogenic activity, have been considered candidates for reducing postmenopausal bone loss. In this study, we examined the effect of dietary equol, a bioactive metabolite of the soy isoflavone daidzein, on equol tissue distribution, bone parameters, and reproductive tissue activity using an adult ovariectomized (OVX) rat model. An 8-wk feeding study was conducted to compare 4 dietary treatments of equol (0, 50, 100, 200 mg/kg diet) in 6-mo-old OVX female Sprague-Dawley rats. A dose response increase in tissue equol concentrations was observed for serum, liver, kidney, and heart, and a plateau occurred at 100 mg equol/kg diet for intestine. In OVX rats receiving 200 mg equol/kg diet, femoral calcium concentration was greater than those receiving lower doses but was still less than SHAM (P < 0.05), and other bone measures were not improved. Tibia calcium concentrations were lower in OVX rats receiving 100 and 200 mg equol/kg diet compared with the OVX control rats. Trabecular bone mineral density of tibia was also lower in equol-fed OVX rats. At this dietary equol intake, uterine weight was higher (P < 0.05) than in other OVX groups but lower than the SHAM-operated intact rats. The 200 mg/kg diet dose of dietary equol significantly increased proliferative index in the uterine epithelium. Dietary equol had no stimulatory effect on mammary gland epithelium. We conclude that in OVX rats, a dietary equol dose that had modest effect on bone also exerts mild uterotropic effects.

SUBMITTER: Legette LL

PROVIDER: S-EPMC2744611 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats.

Legette Leecole L LL Martin Berdine R BR Shahnazari Mohammad M Lee Wang-Hee WH Helferich William G WG Qian Junqi J Waters David J DJ Arabshahi Alireza A Barnes Stephen S Welch Jo J Bostwick David G DG Weaver Connie M CM

The Journal of nutrition 20090826 10

Soy isoflavones and their metabolites, with estrogenic activity, have been considered candidates for reducing postmenopausal bone loss. In this study, we examined the effect of dietary equol, a bioactive metabolite of the soy isoflavone daidzein, on equol tissue distribution, bone parameters, and reproductive tissue activity using an adult ovariectomized (OVX) rat model. An 8-wk feeding study was conducted to compare 4 dietary treatments of equol (0, 50, 100, 200 mg/kg diet) in 6-mo-old OVX fema ...[more]

PMID: 19710157

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Project description:Chronic estrogen replacement in ovariectomized rats attenuates food intake and enhances c-Fos expression in the suprachiasmatic nucleus (SCN), specifically during the light phase. S-equol, a metabolite of daidzein, has a strong affinity for estrogen receptor (ER)-β and exerts estrogenic activity. The purpose of the present study was to elucidate whether S-equol exerts an estrogen-like anorectic effect by modifying the regulation of the circadian feeding rhythm in ovariectomized rats. Ovariectomized female Wistar rats were divided into an estradiol (E2)-replaced group and cholesterol (vehicle; Veh)-treated group. These animals were fed either a standard diet or an S-equol-containing diet for 13 days. Then, the brain, uterus, and pituitary gland were collected along with blood samples. In the rats fed the standard diet, E2 replacement attenuated food intake (P < 0.001) and enhanced c-Fos expression in the SCN (P < 0.01) during the light phase. Dietary S-equol supplementation reduced food intake (P < 0.01) and increased c-Fos expression in the SCN (P < 0.01) in the Veh-treated rats but not in the E2-replaced rats during the light phase. Dietary S-equol did not alter ER-α expression in the medial preoptic area or the arcuate nucleus, nor did dietary S-equol affect pituitary gland weight or endometrial epithelial layer thickness. By contrast, E2 replacement not only markedly decreased ER-α expression in these brain areas (P < 0.001) but also increased both the pituitary gland weight (P < 0.001) and the endometrial epithelial layer thickness (P < 0.001). Thus, dietary S-equol acts as an anorectic by modifying the diurnal feeding pattern in a manner similar to E2 in ovariectomized rats; however, the mechanism of action is not likely to be mediated by ER-α. The data suggest a possibility that dietary S-equol could be an alternative to hormone replacement therapy for the prevention of hyperphagia and obesity with a lower risk of adverse effects induced by ER-α stimulation.

Project description:Nacre has emerged as a beneficial natural product for bone cells and tissues, but its effect was only studied by gavage in the ovariectomized mouse model. We sought to assess the antiosteoporotic effect of nacre through a nutritional supplementation in the ovariectomized rat model. Sixteen-week-old female Wistar rats were either Sham-operated or bilateral ovariectomized (OVX) and then fed with standard diet (Sham and OVX groups) or standard diet supplemented with either 0.25% CaCO3 or nacre (OVX CaCO3 and OVX Nacre group, respectively) for 28 days (n = 10/group). The bone microarchitecture was assessed at appendicular and axial bones by micro-computed tomography (μCT). Histomorphometric analysis was performed to determine cellular and dynamic bone parameters. Bone metabolism was also evaluated by biochemical markers and gene expression levels. Nacre-based diet prevented the OVX-induced bone loss better than that of the CaCO3 supplement, given the significant changes in trabecular bone volume fraction (BV/TV) both at the femoral distal metaphysis (difference, 35%; p = 0.004) and at the second lumbar spine (difference, 11%; p = 0.01). Trabecular osteoclast surfaces (Oc.S/BS) were also 1.5-fold lower at the tibial proximal metaphysis in OVX Nacre group compared with OVX CaCO3 group (p = 0.02). By principal component analysis (PCA), OVX Nacre group formed a cluster away from OVX group and with a trend closest to Sham group. These data were consistent with biological measurements demonstrating a positive profile related to nacre supplementation, which blunted an increase in serum CTX level and enhanced serum P1NP secretion 14 days post-OVX compared with CaCO3 supplementation. Bmp2 mRNA expression in OVX Nacre group was +1.76-fold (p = 0.004) and +1.30-fold (p = 0.20) compared with OVX and OVX CaCO3 groups, respectively. We conclude that supplementation with nacre could effectively limit bone loss induced by estrogen deficiency just after OVX in rats by modulating the negative imbalance of bone turnover. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Project description:Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25?M H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used.

Dataset Information

Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats.

Publications

Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats.

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