Monthly Archives: August 2013

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

Quercetin Inhibits Bone Loss Diabetic Rats

Abstract

Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia.

Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5mg/kg, 30 mg/kg and 50mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia.

Liang W, Luo Z, Ge S, Li M…
Eur. J. Pharmacol. Nov 2011
PMID: 21914440

Quercetin Actions In Vitro

Abstract

Quercetin, a potent suppressor of NF-κB and Smad activation in osteoblasts.

Osteoclasts, the bone resorbing cells of the body, form when osteoclast precursors are exposed to the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL), a process requiring induction of NF-κB signaling. Quercetin is a ubiquitous plant-derived flavonoid with well documented anti-inflammatory properties, in part, a consequence of its capacity to downmodulate the NF-κB signal transduction pathway. Consistent with this mechanism of action quercetin is reported to suppress osteoclastogenesis in vitro and prevent bone loss in ovariectomized mice in vivo. By contrast, the effect of quercetin on osteoblasts, the cells responsible for bone formation, is contradictory with conflicting reports of inhibition as well as stimulation. Given our previous reports that NF-κB antagonists promote osteoblast differentiation and activity, we compared the effects of quercetin on osteoclast and osteoblast differentiation and on NF-κB signal transduction in vitro. As expected, quercetin potently suppressed osteoclastogenesis and NF-κB activation induced by RANKL in osteoclast precursors. However, the same doses of quercetin had no effect on osteoblast mineralization, and failed to significantly alleviate the inhibitory effect of NF-κB-induced by TNFα, even though quercetin potently suppressed NF-κB activation in these cells. This apparent contradiction was explained by the fact that addition to its anti-NF-κB activity, quercetin also potently antagonized both TGFβ and BMP-2-induced Smad activation in osteoblast precursors. Taken together our data suggest that multiple competing actions of quercetin mediate both stimulatory and inhibitory actions on osteoblasts with the final physiological effect likely a function of the net balance between these stimulatory and inhibitory effects.

Yamaguchi M, Weitzmann MN
Int. J. Mol. Med. Oct 2011
PMID: 21769418

Vitamin D + Genistein + Quercetin + Resveratrol in Ovariectomized Rats

Abstract

Preventing bone loss and weight gain with combinations of vitamin D and phytochemicals.

Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D-alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.

Lai CY, Yang JY, Rayalam S, Della-Fera MA…
J Med Food Nov 2011
PMID: 21663481

Quercetin Inhibits Bone Loss Without Affecting Osteoclasts or Estrogen Receptors in Ovariectomized Mice

Abstract

Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice.

Quercetin is a major dietary flavonoid found in onions and other vegetables, and potentially has beneficial effects on disease prevention. In the present study, we demonstrate for the first time the effects of dietary quercetin on bone loss and uterine weight loss by ovariectomy in vivo. Female mice were ovariectomized (OVX) and were randomly allocated to 3 groups: a control diet or a diet with 0.25% (LQ) or 2.5% quercetin (HQ). After 4 weeks, dietary quercetin had no effects on uterine weight in OVX mice, but bone mineral density of the lumbar spine L4 and femur measured by peripheral quantitative computed tomography (pQCT) was higher in both the sham and the HQ groups than in the OVX group. Histomorphometric analysis showed that the HQ group restored bone volume (BV/TV) completely in distal femoral cancellous bone, but did not reduce the osteoclast surface area and osteoclast number when compared with the OVX group. In in-vitro experiments using mouse monocyte/macrophage cell line RAW264.7 cells, however, quercetin and its conjugate, quercetin-3-O-beta-D: -glucuronide dose-dependently inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation, and the RANKL-stimulated expression of osteoclast related genes was also inhibited by quercetin. The luciferase reporter assay showed that quercetin did not appear to have estrogenic activity through estrogen receptors. These results suggest that dietary quercetin inhibits bone loss without effect on the uterus in OVX mice and does not act as a potent inhibitor of osteoclastogenesis or as a selective estrogen receptor modulator in vivo.

Tsuji M, Yamamoto H, Sato T, Mizuha Y…
J. Bone Miner. Metab. 2009
PMID: 19495926

Interesting, I wonder how it works if it doesn’t inhibit osteoclasts in vivo and isn’t estrogenic?

Ginkgo (Kaempferol and Quercetin) Restores Bone Mass in Ovariectomized Rats

Abstract

Effects of Egb 761 on bone mineral density, bone microstructure, and osteoblast function: Possible roles of quercetin and kaempferol.

The effects of standardized and concentrated extract of Ginkgo biloba, Egb 761, were studied on estrogen deficiency-induced bone loss in ovariectomized (OVx) rats rendered osteopenic. Upon osteopenia development, Egb 761 was administered at a dose of 100mgkg(?1)day(?1) by oral gavage to OVx rats whereas control group received vehicle. Following 5 weeks of treatment, the OVx+Egb 761 group (n=12) of rats exhibited significantly higher whole body BMD and lower bone turnover markers (serum alkaline phosphatase and osteocalcin) than OVx rats that were given vehicle (n=12). BMD levels in excised bones were also found to be higher in both trabecular (most robustly in lumbar vertebrae) and cortical bones of OVx+Egb 761 compared with OVx+vehicle group. Egb 761 did not exhibit estrogen agonistic activity at the uterine level. Microcomputed tomography demonstrated that OVx+Egb 761 group had better bone microarchitectural parameters compared with OVx+vehicle group. Moreover, OVx+Egb 761 group had higher femoral mRNA levels of osterix, type I collagen and osteocalcin compared with OVx+vehicle group. Determination of levels of three flavonoids of Egb 761, that are known to have bone conserving property, in serum and bone marrow suggests that kaempferol and quercetin, and not rutin, likely mediate the beneficial actions observed with Egb 761 treatment. These results show for the first time that oral administration of Egb 761 restores bone mass in aged OVx rats.

Trivedi R, Kumar A, Gupta V, Kumar S…
Mol. Cell. Endocrinol. Apr 2009
PMID: 19356626

Quercetin Protects Human Osteoblasts Cells Exposed to Cigarette Smoke

Abstract

Quercetin protects primary human osteoblasts exposed to cigarette smoke through activation of the antioxidative enzymes HO-1 and SOD-1.

Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS). The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM) rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.

Braun KF, Ehnert S, Freude T, Egaña JT…
ScientificWorldJournal 2011
PMID: 22203790 | Free Full Text

Almonds Increase Bone Mass and Inhibit Osteoclasts

Abstract

Postprandial effects of almond consumption on human osteoclast precursors–an ex vivo study.

Consumption of almonds has been associated with increased bone mineral density, but the direct effects of almonds on bone cells are not known. We determined whether serum obtained following the consumption of a meal containing 60 g of almonds affects human osteoclast formation, function, and gene expression in vitro. Human osteoclast precursors were cultured in medium containing 10% serum obtained from 14 healthy subjects at baseline and 4 hours following the consumption of 3 test meals containing almonds, potatoes, and rice and balanced for macronutrient composition. Osteoclast formation was determined by the number of tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells, and osteoclast function was assessed by measuring TRAP activity in the culture medium and calcium released from OsteoAssay (Lonza Walkersville, Walkersville, MD, USA) plates. The expression of cathepsin K, receptor activator of nuclear factor kB, and matrix metalloproteinase-9 genes was measured by real-time reverse transcriptase-polymerase chain reaction. Compared with serum obtained at baseline, serum obtained 4 hours following the consumption of the almond meal reduced osteoclast formation by approximately 20%, TRAP activity by approximately 15%, calcium release by approximately 65%, and the expression of cathepsin K, receptor activator of nuclear factor kB, and matrix metalloproteinase-9 by 13% to 23%. No effects were observed with serum obtained from the other test meals. Serum obtained 4 hours following the consumption of an almond meal inhibits osteoclast formation, function, and gene expression in cultured human osteoclast precursors, and provides evidence for a positive effect of almonds on bone health.

Platt ID, Josse AR, Kendall CW, Jenkins DJ…
Metab. Clin. Exp. Jul 2011
PMID: 20947104