Tag Archives: positive

Quercetin and Rutin Inhibit Resorption by Their Estrogen Receptor Proteins

Abstract

Modulation of osteoclastogenesis in porcine bone marrow cultures by quercetin and rutin.

Flavonols, in contrast to soybean isoflavones, are the most abundant phytoestrogens in western diets, being present in onions, beans, fruits, red wine, and tea. They may protect against atherosclerosis, inhibit certain cancer cell types, and reduce bone resorption. The most widely distributed flavonol is quercetin, which occurs mainly as its glycoside, rutin, but data are very scarce regarding the precise mechanism of action of these compounds on bone-resorbing cells at concentrations similar to those detected in human plasma. We have therefore investigated the effects of nanomolar concentrations of quercetin and rutin on the development and activity of osteoclasts in vitro compared with the effects of 17beta-estradiol. Nonadherent porcine bone marrow cells were cultured on dentine slices in the presence of 10 nM 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), with or without 10 nM quercetin, 10 nM rutin or 10 nM 17beta-estradiol for 11 days. Multinuclear TRAP+ cells that resorbed dentine (osteoclasts) developed in the presence of 1,25(OH)2D3, but their number was significantly reduced by quercetin, rutin, and 17beta-estradiol (P < 0.05). Like 17beta-estradiol, both flavonols also significantly reduced resorption (P<0.05) as assessed by the size of pits resorbed on dentine slices. Osteoclasts and osteoclast progenitors contained estrogen receptor alpha (ERalpha), ERbeta, and RANK proteins. Both flavonols increased nuclear ERbeta protein and decreased ERalpha protein of osteoclast progenitors. Moreover, rutin reduced RANK protein, whereas 17beta-oestradiol and quercetin promoted apoptosis by cleavage of caspase-8 and caspase-3. All the effects of flavonols were reversed by 1 microM ICI 182,780, an estrogen antagonist. Thus, the anti-resorbing properties of flavonols are mainly mediated by ER proteins through the inhibition of RANK protein or the activation of caspases.

Rassi CM, Lieberherr M, Chaumaz G, Pointillart A…
Cell Tissue Res. Mar 2005
PMID: 15688188

Hesperidin Prevents Bone Loss in Orchidectomized Mice

Abstract

Hesperidin Prevents Androgen Deficiency-induced Bone Loss in Male Mice.

The purpose of this study was to examine whether hesperidin inhibits bone loss in androgen-deficient male mice. Male ddY mice aged 7 weeks underwent either a sham operation or orchidectomy (ORX) and were divided into five groups: a sham-operated group fed a control diet (Sham) based on AIN-93G formulation with corn oil instead of soy bean oil, an ORX group fed the control diet (ORX), a group fed the control diet containing 0.5% hesperidin (ORX + H), a group fed the control diet containing 0.7% α-glucosylhesperidin (ORX + αG), and a group fed the control diet containing 0.013% simvastatin (ORX + St). Four weeks after intervention, ORX mice showed a striking decrease in seminal vesicle weight, which was not affected by the administration of hesperidin, α-glucosylhesperidin, or simvastatin. Femoral BMD was significantly reduced by ORX, and bone loss was inhibited by the administration of hesperidin, α-glucosylhesperidin or simvastatin. Histomorphometric analysis showed that the bone volume and trabecular thickness were significantly lower, and the osteoclast number was higher in the distal femoral cancellous bone in the ORX group than in the Sham group, and these were normalized in the ORX + H, ORX + αG and ORX + St groups. These results indicate that hesperidin inhibited bone resorption and hyperlipidemia, in ORX mice, and the preventive effect was stronger than that observed in ovariectomized mice in our previous study.

Chiba H, Kim H, Matsumoto A, Akiyama S…
Phytother Res May 2013
PMID: 23674260

Hesperidin Inhibits Osteopenia in Rats

Abstract

Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats.

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.

Horcajada MN, Habauzit V, Trzeciakiewicz A, Morand C…
J. Appl. Physiol. Mar 2008
PMID: 18174393 | Free Full Text

Resveratrol Improves Bone After Calorie Restriction in Rats

Abstract

Effect of catch-up growth by various dietary patterns and resveratrol intervention on bone status.

Catch-up growth (CUG) after food restriction can increase the risks for insulin resistance-related diseases, and to our knowledge, no previous studies have addressed how bone is influenced by CUG when refeeding diet content differs. The objective of this study was to investigate the bone status resulting from CUG induced by varying refeeding dietary patterns, and to assess the potential influencing factors and the effect of resveratrol on bone status during CUG. Experimental rats were randomly divided into five groups: normal chow (NC) group; CUG group (CUG, containing two subgroups, respectively, refeeding with normal chow or high-fat diet); high-fat diet (HF) group; and resveratrol intervention groups (CUGE and HFE). Bone parameters were detected by dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor (TNF)-α, body weight and food intake were also recorded. Our results showed that food restriction induced a significant decrease in bone parameters. Eight-week CUG by normal chow had a greater degree of improvement in bone mineral density than high-fat diet, and even returned to normal level similar to NC. Bone parameters were elevated in varying degrees in the HF group compared with the NC group. In the resveratrol intervention groups, bone parameters significantly increased. Furthermore, bone parameters were inversely related with serum TNF-α concentrations, but showed positive correlation with body weight. In conclusion, the study shows that CUG can partially reverse the deleterious effects of caloric restriction on bone health, especially in the refeeding with normal chow group. Moreover, resveratrol has a protective effect on bone status during the period of CUG. Serum TNF-α levels and body weight also seem to play an important role in regulating bone parameters.

Chen LL, Wang SX, Dai Y, Buckoreelall P…
Exp. Biol. Med. (Maywood) Mar 2012
PMID: 22442358

Resveratrol + Enalapril Improves Microcirculation and Prevents Microfractures in Rats

Abstract

[Comparative evaluation of the osteoprotective effects of resveratrol and resveratrol/enalapril combination in the treatment of experimental osteoporosis].

The osteoprotective effect of resveratrol and a combination of resveratrol with enalapril has been investigated in white Wistar female rats with experimental osteoporosis. It is established that, in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of the osteal tissue is developed, resulting in the occurrence of osteoporosis. Resveratrol and the combination of resveratrol with enalapril prevented depression of the microcirculation level in the osteal tissue, thus preventing the thinning of osteal trabecules and preventing their microfractures.

Faĭtel’son AV, Koklina NIu, Gudyrev OS, Dubrovin GM…
Eksp Klin Farmakol 2012
PMID: 22834128

Resveratrol Preserves Bone Mass, Structure, and Strength in Inactive Rats

Abstract

Resveratrol supplementation preserves long bone mass, microstructure, and strength in hindlimb-suspended old male rats.

Resveratrol has gained popularity as an “anti-aging” compound due to its antioxidant and anti-inflammatory properties. Few studies have investigated the role of resveratrol supplementation in the prevention of age-related bone loss and skeletal disuse despite increased inactivity and age-related bone loss in the elderly. The objective of the study was to investigate the effect of resveratrol supplementation on disuse and age-related bone loss. Old (age 33 months) Fischer 344 × Brown Norway male rats were provided either trans-resveratrol (12.5 mg/kg bw/day) or deionized distilled water by oral gavage for 21 days. Rats were hindlimb-suspended (HLS) or kept ambulatory (AMB) for 14 days. Both femora and tibiae were collected. Bone mass was measured by dual-energy X-ray absorptiometry and bone microstructure was determined by micro-computed tomography. HLS of old male rats accelerated loss of bone mineral content, decreased trabecular bone volume per unit of total volume, and increased trabecular separation. Resveratrol supplementation ameliorated bone demineralization and loss of bone microarchitecture in HLS old male rats. The peak force measured by the three-point bending test was reduced (P = 0.007) in HLS/control compared to AMB/control rats. Resveratrol supplementation ameliorated HLS-induced loss of femur strength. Plasma osteocalcin and alkaline phosphatase was higher (P < 0.04) and C-reactive protein was lower (P = 0.04) in old male rats given resveratrol. The bone protective effects of resveratrol appeared to be mediated through increased osteoblast bone formation, possibly due to reduced inflammation. Based on the results, resveratrol supplementation appeared to provide a feasible dietary therapy for preserving the skeletal system during disuse and age-related bone loss.

Durbin SM, Jackson JR, Ryan MJ, Gigliotti JC…
J. Bone Miner. Metab. May 2013
PMID: 23686002

8-Prenylnaringenin > Genistein for Preventing Osteoporosis in Ovariectomized Rats; Resveratrol Has no Effect

Abstract

Comparison of the phytohormones genistein, resveratrol and 8-prenylnaringenin as agents for preventing osteoporosis.

As the average age of society increases, identifying and preventing osteoporosis becomes more important. According to the results of the Women’s Health Initiative study, substitution of estradiol is not recommended in hormone replacement therapy (HRT), although phytoestrogens might be a safe alternative. In this study, the osteoprotective effects of genistein (Gen), resveratrol (Res) and 8-prenylnaringenin (8PN) were evaluated by analysing bone biomechanical strength and bone mineral density. After ovariectomy, 88 female rats received soy-free food (C), and according to their grouping, were fed estradiol (E), GEN, RES or 8PN for 12 weeks. The phytohormones were given in two dosages. To analyse the osteoprotective effects of the tested substances, bone biomechanical properties and bone mineral density (BMD) were evaluated on the upper tibial metaphysis. Bone biomechanical properties were significantly improved after treatment with E (F (max): 90.6 N) and 8PN (85.0 N) compared to GEN (76.0 N), RES (72.6 N) and C (76.6 N). Bone biomechanical properties with 8PN (yL: 55.7 N) supplementation reached a level similar to that seen after E (49.3 N) supplementation. Treatment with GEN (38.5 N) was not as effective as E and 8PN, but demonstrated improved biomechanical properties compared to C (40.1 N) and RES (36.3 N). E (Cn.Dn. 217 mg/cm (3)) and 8PN (165 mg/cm3) showed superior results in the analysis of bone mineral density compared to C (112 mg/cm (3)). GEN (164 mg/cm (3)) also demonstrated superior results, though not as good as E and 8PN. RES (124 mg/cm (3)) revealed no effect on bone density. Treatment with 8PN resulted in very good biomechanical properties and showed an increased BMD. GEN had a smaller effect on bone biomechanical strength, while RES did not have an effect on bone biomechanical strength or BMD. Therefore, 8PN might be a safe alternative for HRT, but further studies are needed.

Sehmisch S, Hammer F, Christoffel J, Seidlova-Wuttke D…
Planta Med. Jun 2008
PMID: 18537073

It is surprising and disappointing that resveratrol had no effect on bone density in this study.

Resveratrol Prevents Bone Loss in Inactive Rats

Abstract

Effect of prior treatment with resveratrol on density and structure of rat long bones under tail-suspension.

Physical inactivity during space flight or prolonged bed rest causes rapid and marked loss of bone mass in humans. Resveratrol, a red wine polyphenol that is currently under study for its therapeutic antioxidant properties, has been shown to significantly modulate biomarkers of bone metabolism, i.e., to promote osteoblast differentiation and to prevent bone loss induced by estrogen deficiency. However, there is no direct evidence supporting its inhibitory effect toward bone loss during physical inactivity. In the present study, effects of resveratrol on bone mineral density (BMD), bone mineral content, and bone structure were examined in the femora and tibiae of tail-suspended and unsuspended rats using X-ray micro-computed tomography (micro-CT). Rats were treated with 400 mg/kg/day of resveratrol for 45 days and half of them were suspended during the last 2 weeks of treatment. Suspension caused a decrease in tibial and femoral BMD and deterioration of trabecular and cortical bone. Bone deterioration during suspension was paralleled by increased bone marrow area, which could be caused by an increase in stromal cells with osteoclastogenic potential or in adipocytes. Resveratrol had a preventive effect against bone loss induced by hindlimb immobilization. In particular, trabecular bone in the proximal tibial metaphysis was totally preserved in rats treated with resveratrol before tail-suspension.

Habold C, Momken I, Ouadi A, Bekaert V…
J. Bone Miner. Metab. Jan 2011
PMID: 20458604

Resveratrol Stimulates Osteocalcin in Rat Cells

Abstract

Estradiol and resveratrol stimulating effect on osteocalcin, but not osteonectin and collagen-1alpha gene expression in primary culture of rat calvarial osteoblast-like cells.

Evidence is available that some endocrine disruptors, acting as selective estrogen receptor modulators (SERMs), interfere with osteoblast differentiation and function. Therefore, we investigated whether 17beta-estradiol, bisphenol-A (BSP), silymarin, genistein, resveratrol, procymidone, linurone and benzophenone-3 (BP3) modulate differentiation of rat calvarial osteoblast-like (ROB) cells in primary in vitro culture. Disruptors were added at day 18 of culture and cells were harvested 48 h later. Real time-PCR revealed that estradiol and resveratrol enhanced osteocalcin mRNA expression in ROB cells, while other disruptors were ineffective. The expression of osteonectin and collagen-1alpha was not affected by any disruptor. Estradiol, resveratrol, genistein and BSP stimulated the proliferative activity of ROB cells. In contrast, procymidone and linurone inhibited the proliferative activity, and silymarin and BP3 were ineffective. The conclusion is drawn that i) only resveratrol is able, like estradiol, to stimulate the specialized functions of ROB cells, and ii) the proliferative activity of ROB cells is more sensitive to endocrine disruptors, some of which could probably act via a mechanism independent of their SERM activity.

Rucinski M, Ziolkowska A, Hochol A, Pucher A…
Int. J. Mol. Med. Oct 2006
PMID: 16964405

Quercetin Completely Prevents Bone Loss from Glucocorticoids in Rats

Abstract

Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate.

Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. The aim of this study was to compare the efficacy of quercetin, a plant-derived flavonoid, with alendronate in the prevention of GIO. Fifty-six Sprague-Dawley rats were randomly distributed among 7 groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg methylprednisolone sodium succinate (MP)/kg body mass; (iii) MP + 40 μg alendronate/kg; (iv) MP + 50 mg quercetin/kg; (v) MP + 40 μg alendronate/kg + 50 mg quercetin/kg; (vi) MP + 150 mg quercetin/kg; and (vii) MP + 40 μg alendronate/kg + 150 mg quercetin/kg. MP and alendronate were injected subcutaneously and quercetin was administered by oral gavage 3 days a week. At the end of the study, femur breaking strength was significantly decreased as a consequence of MP injection. This decrease was completely compensated for in groups receiving 50 mg quercetin/kg plus alendronate, and 150 mg quercetin/kg with or without alendronate. Quercetin noticeably elevated osteocalcin as a bone formation marker, while alendronate did not show such an effect. In addition, administration of 150 mg quercetin/kg increased femoral trabecular and cortical thickness by 36% and 22%, respectively, compared with the MP-treated group. These data suggest that 150 mg quercetin/kg, alone or in combination with alendronate, can completely prevent GIO through its bone formation stimulatory effect.

Derakhshanian H, Djalali M, Djazayery A, Nourijelyani K…
Can. J. Physiol. Pharmacol. May 2013
PMID: 23656499