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

Review: Resveratrol Osteogenic Effects In Vitro

Abstract

Osteogenic effects of resveratrol in vitro: potential for the prevention and treatment of osteoporosis.

There are a number of pharmacological agents for the treatment of bone mineral loss and osteoporosis. Hormone replacement therapy (HRT) with estrogen is an established treatment, but it has several adverse side effects and can increase the risk of cancer, heart disease, and stroke. There is increasing interest in nutritional factors and naturally occurring phytochemical compounds with the potential for preventing age-related and postmenopausal bone loss. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoestrogen with osteogenic and osteoinductive properties. It can modify the metabolism of bone cells and has the capacity to modulate bone turnover. This paper provides an overview of current research on resveratrol and its effects on bone cells in vitro, highlighting the challenges and opportunities facing this area of research, especially in the context of providing nutritional support for postmenopausal women who may not benefit from HRT and older patients with various forms of arthritis, metabolic bone disease, and osteoporosis.

Mobasheri A, Shakibaei M
Ann. N. Y. Acad. Sci. Jul 2013
PMID: 23855466

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

Review: Resveratrol + Genistein + Quercetin + Vitamin D Synergy

Abstract

Synergism between resveratrol and other phytochemicals: implications for obesity and osteoporosis.

Resveratrol, a phytoalexin, has gained much attention recently due to its effects on sirtuins. While the anti-cancer properties of resveratrol have been extensively investigated, the anti-adipogenic and osteogenic effects of resveratrol are also gaining considerable interest. The finding that resveratrol supplementation mimics caloric restriction prompted researchers to study the effects of resveratrol on lipid metabolism. Mesenchymal stem cells are the precursors for both adipocytes and osteoblasts. In the aging population, differentiation to adipocytes dominates over the differentiation to osteoblasts in bone marrow, contributing to the increased tendency for fractures to occur in the elderly. Thus, an inverse relationship exists between adipocytes and osteoblasts in the bone marrow. Resveratrol acts on several molecular targets in adipocytes and osteoblasts leading to a decrease in adipocyte number and size and an increase in osteogenesis. Furthermore, resveratrol in combination with genistein and quercetin synergistically decreased adipogenesis in murine and human adipocytes. A recent in vivo study showed that phytochemicals including resveratrol in combination with vitamin D prevented weight gain and bone loss in a postmenopausal rat model. Therefore, combinations of resveratrol with other phytochemicals may lead to potential novel potent therapies for both obesity and osteoporosis.

Rayalam S, Della-Fera MA, Baile CA
Mol Nutr Food Res Aug 2011
PMID: 21538845

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

Quercetin Improves Bone Strength in Cirrhotic Rats

Abstract

Quercetin improves bone strength in experimental biliary cirrhosis.

Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. Methods: Twenty-four male Sprague-Dawley rats aged 6-7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. Results: Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. Conclusion: These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.

Derakhshanian H, Ghadbeigi S, Rezaian M, Bahremand A…
Hepatol. Res. Apr 2013
PMID: 22882531

Rutin Effects Likely from Quercetin

Abstract

[Comparative study on effects of rutin and quercetin on metabolism in osteoblast cells].

To investigate the mechanism of rutin and its aglycone (quercetin) in preventing and treating osteoporosis and their effects on stimulating bone formation were studied comparatively in osteoblast cells.
The effects of rutin and quercetin on the proliferation, differentiation and mineralization were studied respectively by using tetrazolium (MTT), alkaline phosphatase (ALP) and mineralized nodules assays in newborn rat calvarial osteoblast (ROB) cells.
Quercetin showed significant stimulatory effects on proliferation and mineralization in ROB cells, so it could promote bone formation. However, rutin could not improve stimulation of bone formation because it increased proliferation and inhibited differentation and had no remarkable influence on ROB cells in vitro.
Rutin showed less activity than quercetin on bone formation in ROB cells in vitro. Therefore the mechanism that some foods and traditional Chinese medicine containing rutin can prevent and treat osteoporosis is that its metaboite in vivo can promote bone formation in ROB cells.

Yang YJ, Yang ZL, Wang DC, Xiao XC…
Zhong Yao Cai May 2006
PMID: 16981462