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#QUERCETIN BenefitsQuercetin and bone health -
The mice were anesthetized for blood collection from the retro-orbital vein and then euthanized. The liver, gastrocnemius, femur, and tibia were removed and collected carefully.
Gait analysis was conducted using a ventral plane videography instrumentation MSI, USA. All mice first ran at least seven adaptive runs as training before being formally recorded.
Stride length, stride length coefficient of variation CV , stride frequency, and gait symmetry were analyzed to assess the ability of dynamic balance. For bone microarchitecture analysis of the trabecular bone, micro-CT Skyscan , Germany was used.
The parameters were set as follows: voxel size 9 μm, voltage 55 kV, and current 70 mA. After completion of the scan, the region of interest ROI was selected from a distance of 0. Th , trabecular number Tb.
N , and trabecular separation Tb. Sp , were measured. The right femurs was collected for the biomechanical three-point bending test and performed on a servohydraulic test system MTS acumen3, USA at 0. The biomechanical parameter of stiffness, maximum load, maximum deflection, and fracture energy were then calculated from displacement and force.
Next, the femur, liver, and muscle were dehydrated by gradient ethanol, and then cleared with xylene solution. Specimens were then embedded in paraffin, and serial sections were generated at 5 µm thickness.
The sections were stained with hematoxylin and eosin. Then sections observe alterations in the bone microstructure through an inverted microscope Leica, DM The red stain represented the muscle fibers and blue stains represented the collagen fibers, and the muscle fiber area and collagen fiber area were calculated.
The gastrocnemius muscle and liver were fixed and embedded in the OCT compound. Next, the slices were placed in Oil Red O solution for 8 min for staining. Finally, the slices were photographed, and the area of the lipid droplet formation was analyzed.
All kits were provided by Nanjing Jin Yibai Biological Technology Company China. The expression serum of testosterone Jin Yibai, JEB , β-isomer of C-terminal telopeptide of type I collagen β-CTX, Jin Yibai, JEB , TRAP Jin Yibai, JEB , IL-6 Jin Yibai, LAH , bone alkaline phosphatase B-ALP, Jin Yibai, JEB , Osteocalcin OCN, Jin Yibai, JEB , insulin-like growth factor-1 IGF-1, Jin Yibai, JEB , and insulin Mercodia, were measured based on the standard sandwich ELISA protocol.
Triglyceride, total cholesterol, high-density lipoprotein HDL , low-density lipoprotein LDL and free fatty acid FFA levels were detected using the automatic biochemical analyzer AU, Beckman. The left tibia, gastrocnemius muscle and liver was lysed in RIPA lysis buffer containing a protease inhibitor cocktail.
The samples were sonicated and incubated on ice for 30 min and then the insoluble material was removed by centrifuging at rpm for 5min. The protein in the supernatant was collected and then quantified by BCA kit Yeasen, ES Subsequently, the gel was transferred onto PVDF membranes with a constant electric current of mA.
After the PVDF membranes were blocked using blocking solution for 15 min, the membranes were incubated with anti-Gprc6a ; SAB, , anti-AMPK ; CST, , anti-p-AMPK ; CST, , anti-RUXN2 ; Proteintech, AP , anti-Osterix ; Abcam, ab , and anti-GAPDH ; Proteintech, AP overnight at 4°C and then incubated with the secondary antibody ; Proteintech, AP for 2 h on a horizontal shaker at normothermia.
Finally, the membrane was moistened using ECL reagent and the image was exposed to obtain the bands. The Hieff qPCR SYBR Green PCR Master Mix Yesaen, ES03 was used for q-PCR analysis. Each value was adjusted using β-actin as the reference. The 2 - ΔΔCt method was used to analyze PCR array results.
The raw data and generated statistics were analyzed using the SPSS software v The data were transformed and presented as the mean ± standard deviation SD and were analyzed using the Kruskal—Wallis one-way analysis of variance ANOVA when the data were not normally distributed.
The GraphPad Prism software 9. Upon orchiectomy, due to the absence of the testes and epididymides, the serum testosterone levels decreased rapidly. Figure 1 Changes in serum levels of testosterone and undercarboxylated osteocalcin uOCN in mice that have undergone orchiectomy. A Serum testosterone levels in the sham-operated sham , model model , low- QL , and high-quercetin groups QH.
B Serum uOCN levels in all treatment and control groups. model group. To measure the bone volume and bone microstructure in mice that underwent orchiectomy, micro-CT scans were employed and the characteristics of the distal femoral trabecular bone were evaluated.
As shown in Figure 2A , the bone trabeculae was significantly lower in the model group than the sham-operated group. Th were higher and trabecular separation Tb.
The distal femoral had lesser bone trabecula and thinner cortical bones in the model group than the sham-operated group. In addition, increased bone trabecula, fewer lipid droplets, and better intertrabecular connectivity were observed in the low- and high-quercetin groups.
These data suggest that after 8 weeks of treatment, bone density improved and the high-dose quercetin effectively increased BMD and improved bone microarchitecture in mice that had undergone orchiectomy. In addition, bone resorption of the distal femoral trabecular bone was observed directly by TRAP staining Figures 3F.
Subsequently, the levels of serum TRAP were measured and the changes after quercetin administration is consistent with TRAP staining Figures 3H. Figure 2 Quercetin induced improvement of bone microstructure in mice that underwent orchiectomy.
A 2D images and 3D reconstruction of the distal femur by micro-computed tomography. B Bone mineral density BMD of the distal femur.
N , trabecular thickness Tb. Th , and trabecular separation Tb. Figure 3 Effects of quercetin on the biomechanical characteristics and capacity for bone resorption in mice that underwent orchiectomy. A—D Changes in the biomechanical characteristics in femur: including the maximum load and deflection, fracture energy, and stiffness.
F Effects of quercetin on the bone resorption in mice that underwent orchiectomy, visualized by TRAP staining. H Changes in serum levels of TRAP in mice that have undergone orchiectomy. Fresh femurs were evaluated using a three-point bending test to determine the biomechanical status of the cortical bone.
The musculoskeletal system is a dynamic system that requires a strong balance. A decreased compliance of the body was observed in the muscle system when the skeletal system was changed. The same trend was observed for low doses of quercetin; however, the increase in stride frequency was not significantly Figure 4B.
These findings suggest that quercetin improves balance motion ability, subsequently preventing falls and reducing the fracture risk often experienced with osteoporosis. Figure 4 Gait analysis in mice that underwent orchiectomy. A The full gait was recorded and segmented into independent gait cycles.
Changes in gait characteristics: including the B stride length, C stride length CV, D stride frequency, and E gait symmetry. The average cross-sectional area of myofibers decreased notably in the model group, along with an obvious broadening of the interstitial spaces among the muscle fibers.
These results indicate that quercetin may promote morphological changes in the gastrocnemius muscle by improving muscle mass and decreasing collagen fiber area and lipid droplets.
Figure 5 Effects of quercetin on morphological changes in the gastrocnemius muscle of mice that underwent orchiectomy. E Oil Red O staining of the gastrocnemius muscle, and F the changes in the area of the lipid droplet.
To determine the impact of quercetin on bone homeostasis in mice that had undergone orchiectomy, markers of bone resorption β-CTX, and IL-6 and bone formation OCN and B-ALP were evaluated using ELISA.
The serum levels of OCN significantly decreased whereas B-ALP increased after orchiectomy Figures 6C, D. Moreover, the mRNA and protein expression of OCN, RUNX2, and Osterix were also analyzed Figures 6E —G.
Figure 6 Effects of quercetin on bone metabolism in mice that underwent orchiectomy. The serum levels of markers of bone resorption including A β-isomerized C-terminal telopeptides β-CTX , B interleukin 6 IL-6 , C bone alkaline phosphatase B-ALP , and D osteocalcin OCN.
E The expression of bone formation proteins in the tibia, including OCN, RUNX2, and Osterix. F Semi-quantification of OCN, RUNX2, and Osterix by Image J software. G The mRNA expression of OCN, RUNX2, and Osterix in tibia.
Histological abnormalities in liver upon orchiectomy and quercetin treatment were evaluated. As shown in Figure 7A , the structure of the liver was normal in the sham-operated group, whereas the fat vacuole, which is a typical sign of fat degeneration, was clearly observed in the model group.
Furthermore, the area of lipid droplets in the model group was markedly enlarged compared to that in the sham-operated group. However, hepatic steatosis was significantly attenuated, and the area of lipid droplets was smaller after quercetin intervention Figures 7B, C.
However, following quercetin treatments, total cholesterol, triglycerides, LDL, and FFA were significantly decreased, whereas HDL was increased in the low- and high-quercetin groups Figures 7D —H.
The mild change in triglycerides and HDL in the low-quercetin group was not statistically significant Figures 7E, F. These results indicated that quercetin effectively alleviated hepatic steatosis and improved lipid metabolism. Figure 7 Effects of quercetin on lipid and glucose metabolism in mice that underwent orchiectomy.
B Oil-Red O staining of the liver, and C the percentage of lipid droplet area analysis. The serum levels of markers of lipid metabolism including D total cholesterol, E triglycerides, F high-density lipoprotein HDL , G low-density lipoprotein LDL , and H free fatty acid FFA.
The serum levels of markers of glucose metabolism including I insulin, and J insulin-like growth factor-1 IGF Figure 8 Changes in lipid and glucose metabolism in mice that underwent orchiectomy after quercetin treatment.
In addition to lipid metabolism, we analyzed the corresponding glucose metabolism. After quercetin treatment, we observed a significant decrease in insulin and an increase in insulin-like growth factor-1 levels in the low- and high-quercetin groups Figures 7I, J. These results indicated that quercetin effectively alleviated hepatic steatosis and improved both glucose and lipid metabolism.
As an essential modulated regulator of metabolism, GPRC6A may play a critical role in osteoporosis. To further elucidate the possible mechanisms by which this occurs, the expression of GPRC6A in the liver and femur was analyzed.
Next, the downstream signaling of GPRC6A, including AMPK and mTOR, was examined in both the liver Figure 9E and femur Figure 9F. These results indicated that quercetin may promote AMPK phosphorylation and inhibit mTOR phosphorylation.
Immunohistochemical staining for GPCR6A and staining quantification in liver A, B and C, D. Expression of GPCR6A in the liver E and bone F evaluated by western blotting assay on the left and semi-quantitative analysis on the right.
Among other symptoms, testosterone deficiency, due to either chronic illnesses or endocrine treatments, can result in bone mineral density BMD decline. Despite its beneficial effects on bone health, testosterone replacement therapy may cause other problems, including decreased sperm production and fertility, cardiovascular disease, and prostate cancer or hyperplasia.
In this study we aimed to determine the bone-protective effects of quercetin in mouse model of testosterone deficiency-induced osteoporosis. In contrast to previous investigations on rats, where osteoporosis manifests at 12 weeks after orchiectomy 22 , we found that it appears at 8 weeks after orchiectomy in mice.
Due to testosterone deficiency, the mice that underwent orchiectomy not only exhibited decreased bone density, bone mass, and imbalance of bone metabolism, but also endocrine hormone disorders.
These results are consistent with clinical presentations and may provide the foundation for subsequent studies. The potential pharmacological effects of quercetin have been extensively explored as dietary constituents.
Due to its antioxidative, anti-inflammatory, and anti-apoptotic effects, it has been clinically applied for the treatment of various diseases 11 — In this study, we found that quercetin increased bone mass and improved bone strength in orchiectomy mice, indicating that quercetin has therapeutic effects on osteoporosis induced by testosterone deficiency.
Furthermore, the effect of quercetin in musculoskeletal system has been described here for the first time. In this study, quercetin was confirmed to significantly promote histological changes by improving the cross-sectional area of the myofibers, decreasing collagen fiber area and lipid droplets in gastrocnemius muscle.
In parallel, gait analysis results showed that quercetin could improve balance motion ability. These findings suggest that quercetin may have potential of reducing the fracture risk often experienced with osteoporosis. Conventionally, testosterone affects bone mass and strength via its conversion to 5α-dihydrotestosterone in peripheral tissues.
Then, 5α-dihydrotestosterone further promotes osteoblast proliferation and inhibits osteoblast apoptosis by interacting with the androgen receptor. When the androgen receptor signaling is blocked, the mice exhibits a series of abnormal musculoskeletal findings, including decreased bone volume and trabecular number Previous studies have found that orchiectomy is often accompanied by decreased levels of testosterone and increased bone loss Similarly, we found that markers for bone resorption, TRAP, β-CTX, and IL-1, were significantly elevated after orchiectomy.
B-ALP is a ubiquitous metalloenzyme that catalyzes the hydrolysis of phosphate esters and generates an organic radical and inorganic phosphate. As a mature and active marker of osteoblasts, B-ALP is involved in bone formation and reflects osteocyte formation and activity status As expected, the serum B-ALP levels increased gradually after orchiectomy.
This suggests that testosterone deficiency impaired osteocyte function, and bone metabolism was in a high bone turnover state. The biochemical marker of bone turnover, OCN, principally reflects the bone formation produced by mature osteoblasts.
In addition to being essential for mineralized bone matrix, OCN also stimulates testosterone biosynthesis via uOCN Additionally, a series of studies reported a close relationship among testosterone and OCN in patients with metabolic disorders 28 — We found in this study that the levels of OCN and uOCN in serum decreased significantly following orchiectomy, which implies that the relationship between testosterone and OCN is not one-way but includes a network or coupling system.
Recent research has shown that the main mechanism by which quercetin increases testosterone is by promoting its synthesis in the Leydig cells Notably, quercetin significantly increased the serum levels of testosterone, OCN, and uOCN after orchiectomy.
On the one hand, the increase in testosterone suggests that quercetin does increase testosterone by promoting synthesis in the adrenal glands, whereas the increase in uOCN reflects, at least in part, that quercetin may also increase testosterone by promoting OCN synthesis.
As a cornerstone of treatment methods, orchiectomy has been widely applied and may be the most crucial cause of accelerated bone loss in prostate cancer Previous studies have suggested that the level of serum testosterone is correlated with long-term survival rate in prostate cancer Nevertheless, the decreasing serum levels of testosterone with orchiectomy were consistent with its clinical presentation after ADT, and quercetin increased testosterone levels in the serum.
This may suggest that elevated serum testosterone levels might increase the possibility of recurrence in patients with prostate cancer. The importance of measuring changes in testosterone levels in patients undergoing ADT is undoubtedly important.
However, a recent systematic review on the relationship between testosterone and prostate cancer reported that low serum levels of testosterone might enhance the risk of prostate cancer These contradictions might have multiple explanations, including the fact that serum testosterone is not equivalent to intraprostatic testosterone, the indeterminate effects of androgen receptors, and the different testosterone measurement sites between serum and intraprostatic region Furthermore, the contraindications for testosterone replacement in prostate cancer have been challenged.
Several studies have suggested that the risk of exogenous testosterone replacement appears to be small and may reduce biochemical recurrence in prostate cancer following a prostatectomy 35 — This finding indicates that there is no additional risk of prostate cancer after quercetin treatment.
Overall, based on the antitumor efficacy, quercetin could improve bone characteristics in osteoporosis due to testosterone deficiency. As a main anabolic steroid hormone, testosterone exerts biological effects by regulating the energy balance to maintain glucose and lipid synthesis Previous studies have shown that testosterone deficiency significantly alters glucose and lipid metabolism.
In a prospective study of patients who received ADT treatment for one year, total testosterone level decreased by In addition to alterations in triglyceride, cholesterol, LDL, and HDL levels, a decrease in FFA levels was also observed in our study.
Consistently with previously reported data 45 , 46 , the elevation of circulating insulin level and lower serum level of IGF-1 indicates that orchiectomy induced insulin resistance.
Testosterone deficiency often accounts for negative effects on lipid and glucose metabolism, and some bone and skeletal metabolism comorbidities may be associated with these changes.
Abnormal bone metabolism can cause disturbed glucose metabolism by reducing the advanced glycation end product AGE Aung and Lee found that inhibiting AGE and regulating glucose homeostasis may promote osteogenic differentiation of bone marrow mesenchymal stem cells BMSCs and improve bone metabolism and mass 47 , A recent study also found that orchiectomy could lead to lipid metabolism disorder, and decreased bone characteristics were improved after testosterone supplementation to decrease blood lipid levels.
These findings show that glucose and lipid metabolic disturbances are risk factors for osteoporosis due to testosterone deficiency. GPRC6A is activated by OCN and testosterone and performs an essential function in the modulation of testosterone and energy metabolism Due to lack of OCN and testosterone, decreased expression of GPRC6A was simultaneously detected in orchiectomy mice.
After knockout of GPRC6A in the hepatocytes, male mice exhibited several metabolic abnormalities, including abnormal glucose levels and increased serum FFA and cholesterol levels Many of our findings are consistent with this study, which may indicate that GPRC6A is a potential therapeutic target for metabolic disorders in orchiectomy mice.
To date, the downstream targets of quercetin-GPRC6A have not yet been identified. Glut 1 and Glut 4 are the major insulin-sensitive glucose transporters, and they have been demonstrated to be stimulated by AMPK and promote glucose transfer into the cell In addition, phosphorylated AMPK alleviates endoplasmic reticulum stress and increases hepatic autophagy to reduce the levels of hepatic cholesterol and triglycerides by inhibiting the phosphorylation levels of mTOR Phosphorylated AMPK could significantly increase osteogenic differentiation by promoting RUNX2 expression and inhibiting PPAR expression, which is an indicator of differentiation from BMSCs to osteoblasts and adipocytes, respectively 52 , We found that GPRC6A was expressed in the bone tissues, and its expression decreased after orchiectomy.
In summary, we first verified the biological function of quercetin in testosterone deficiency-induced osteoporosis. These findings may act as a foundation for the further examination of quercetin as great potential drug for osteoporosis induced by testosterone deficiency.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The animal study was reviewed and approved by Experimental Animal Center of Nanjing University of Chinese Medicine. JS and WD conceived and designed the experiment, analyzed the data and interpreted the results and developed the manuscript.
YP, PT, CW, XL, and QH collaborated in the pharmacological experiments. YM and YG supervised the work and proofread the manuscript.
All authors contributed to the article and approved the submitted version. This work was supported by National Natural Science Foundation of China No. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Halpern JA, Brannigan RE. Testosterone Deficiency. JAMA doi: PubMed Abstract CrossRef Full Text Google Scholar. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe.
J Clin Endocrinol Metab — Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results From the Massachusetts Male Aging Study.
Kim DK, Lee HS, Park JY, Kim JW, Ahn HK, Ha JS, et al. Androgen-Deprivation Therapy and the Risk of Newly Developed Fractures in Patients With Prostate Cancer: A Nationwide Cohort Study in Korea.
Sci Rep Qaseem A, Horwitch CA, Vijan S, Etxeandia-Ikobaltzeta I, Kansagara D, Forciea MA, et al. Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians. Ann Intern Med — Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al.
Lessons From the Testosterone Trials. Endocr Rev — Ye J, Zhai X, Yang J, Zhu Z. Association Between Serum Testosterone Levels and Body Composition Among Men 20—59 Years of Age.
Int J Endocrinol Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, et al. Endogenous Sex Hormones and Incident Fracture Risk in Older Men: The Dubbo Osteoporosis Epidemiology Study. Arch Intern Med — Harman SM. Thank you for the bone appetite cook book!
joy markman. So my Prof. Vivian good luck to you — you are doing a great job. Please answer me at my email address. I would be willing to stock your vitamins for South Africa if you would like. Thanks so much for being there.
Best Joy Markman. Helen Kroll. Thanks, Helen. Customer Support. Thanks for your interest, Helen! hi vivian, thank you for your great health informations; they are very interesting and helpful. I read them because i have the beginning of osteosporosis, and sometimes i feel very depressed.
Have a great day, and hi to every one! My friend had your book which I was looking at. She told me that you have sales and sell books for half price that might be a little wrinkled. Please let me know when the next time will be that you will do that again.
Thank you very much, Roberta. I follow, mostly Dr. Early in Dec. last year, I broke both sides of my left ankle and discovered even worse Osteoporosis than I expected. Joyce M. Supplement memory with Index Cards; Write SOBones foods on card with A for Acid;or B for base alkaline beside names ofFruit, Veggie, Nuts, Grains,etc— carry to store when shop each time.
Vivian Goldschmidt, MA. Regular yogurt has three times as much calcium than Greek yogurt and is therefore great for people who need more calcium in their diet. Greek yogurt has a lower potassium content than regular yogurt. Every 6 oz serving of Greek yogurt contains around mg of potassium whereas regular yogurt contains around mg of potassium.
How much quercetin does one need to take a day to obtain the benefits? Such as one or two apples a day or what amount of foods do you need to eat daily to get the benefit of quercetin? Quercetin is a bioflavonoid common in the plant kingdom, especially high in onions, red wine, and green tea.
Ideally, we should be drinking 5 cups a day. Too many for me. JOYCE CORMACK. I drink one tea bag in 2 cups of water, hope to move up to one cup water to one teabag. Is loose tea that you brew any better than tea bags for these nutrients?
I get the loose tea for brewing. It is tastier and fresher. Cup for cup, kale is the king of calcium it contains three times more than spinach. The crimson veggie is a rich source of inulin, a carbohydrate that naturally enhances calcium absorption in the intestines, according to a recent study in the journal of lost in the paste.
I forgot to add that the loose tea I buy, the leaves are actually green in color. Leslie Ms. I Also Take Evening Primrose In A Soft Gel Form. NANCY RAIN. This has helped very little and is costly to continue.
Is going to try steroid injections next. Can you advise us on any treatment for the relief of pain. Thank you. Clara Mae Watrous. Hi Vivian, Very interesting about quercetin and the foods that are high in it. I have a question. I want to get your program as soon as I gather some money to do so.
Clara Mae. So stay tuned! Hi, My question is what, if any, muli-vitamin is recommended. I purchased the SaveOurBones program last year, and am taking an AlgaeCal based calcium supplement, with D3, K2, etc.
But Vivian recommends many other Vitamins and minerals to take. I am no fan of a multivitamin. There is always too much vitamin A, the synthetic kind, in them. Vitamin A, the synthetic type, keeps us from absorbing D. We get so much A from our vegetables, natural A, and our body knows how to deal with it properly.
Dianne, I am not currently recommending any particular brand of multivitamin…but the Program does contain an extensive list of Foundation Supplements, so you should have all the information you need to choose a good one.
Nancy Pulecio. Dear Vivian, you are so wonderful sharing with all of us all your knowledge. There are not enough words to thank you. Every day when I look into your e-mail I feel you are like my doctor telling me what to do with my osteoporosis and I am sure that in a year since I started following your guidance I will be WELL!
Thanks always thanks!!! Today, February 20, , I read your latest suggestion for good bone health. You suggested that we use the antioxidant called, Quercetin. Is it a new finding? This information simply underscores the healthful nature of the Save Our Bones diet.
Yes, blueberries and cranberries are acidifying, Andrea; but that does not mean they are off-limits. Raymonde Savoie.
I know Quercetin very well from having studied it as part of my herbs and herbal remedies that I make from wild herbs. One free and significant source of Quercetin is found in the leaves of the quite deceivingly ordinary plant, Evening Primrose, Oenothera biennis.
The whole plant was once used by indigenous peoples in North America, and as many know, the seeds of this plant are the base for Evening Primrose Oil, with potent GLA that helps an array of conditions, among them PMS and ADD.
If you collect the leaves for consumption, you must make sure that the plant does not grow within short distance of any parking lot, public or private roads, etc. because you risk ingesting the pollution from vehicle exhaust fumes. Luckily, this plant grows in many habitats, so you are bound to find it somewhere where it is safe to collect it.
Evening Primrose is a biennial plant, so the first year you will find only the flat rosette of leaves growing in a circle close to the ground. The second-year plants have the distinctive stalks and the typical yellow flowers that only open on cloudy days or after sunset, giving it its common name.
This plant is literally my champion of all herbs! Thank you so much for your contribution, Raymonde! Thanks again for this great research information. Have a great day everyone! Save Our Bones Bulletin: New Imaging Technology Reveals Activity Of Osteoclasts; Protein Found To Facilitate Bone Resorption; Debunking The 10, Steps Myth.
Save Our Bones Bulletin: Gut Microbiome Linked To Bone Loss; Strawberries Found To Improve Cognitive Function; Mollusk-Derived Supplement Improved Bone Density In Mice.
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By Vivian Goldschmidt, MA The Antioxidant That Builds Your Bones And So Much More. Quercetin: A Nutritional Powerhouse That Helps Increase Bone Density The antioxidant quercetin has an indirect but very powerful effect on your bones. These stabilizing substances, of course, are antioxidants.
How The Antioxidant Quercetin Helps Quercetin is one of many antioxidants, but it deserves special mention because its positive effects on the body go beyond the disruption of the oxidative cycle mentioned above. The Role Of Stress In Your Bone Health Chronic stress is debilitating for many body systems, including your bones.
The adrenal glands produce cortisol as part of this process. Health Benefits Of Quercetin Beyond Your Bones In addition to the stress-reducing effects of quercetin, research has also shown that this antioxidant aids other body systems too.
For example… Quercetin balances blood pressure according to a study published in the Journal of Nutrition. Participants in the study experienced balanced arterial pressure after taking quercetin supplements. Preliminary findings suggest that quercetin inhibits the release of histamines.
Quercetin is a major dietary flavonoid found in healty and other vegetables, Quality natural weight management potentially Nutrient supplements for athletes beneficial effects Quercetin and bone health disease helth. In the present study, we demonstrate Quedcetin the first time the effects heslth dietary quercetin Quercetin and bone health bone bpne and Hyperglycemia and neuropathy weight loss by heatlh in Quercstin. Female mice nad ovariectomized OVX and were randomly bbone to 3 groups: Nutrient timing for satiety control diet or a diet with 0. 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. 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. This is a preview of subscription content, log in via an institution to check access.
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In addition to the stress-reducing effects of quercetin, research has also shown that this antioxidant aids other body systems too.
For example…. Clearly, quercetin performs multiple health-related tasks in the body, which makes it an ideal natural solution to overall health and specific health issues. Compare this approach to individual medicines that target one symptom and health problem at a time, such as over-the-counter OTC antihistamines.
Inevitably, such medications have side effects. Take, for example, the OTC antihistamine Claritin loratadine — side effects include:. This is just one example of many. Instead of using a synthetic halth in isolation, you should consume whole foods to obtain an array of synergistic compounds that build your overall health.
Here are the richest sources of this antioxidant, and all the synergistic substances that are also in these foods work together to promote optimal health. With the exception of chocolate, all of these foods are Foundation Foods in the Osteoporosis Reversal Program.
This is why the Osteoporosis Reversal Program delves into the nutritional, bone-building effects of foods as part of its all-natural, drug-free approach. I know I would. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis. Toxicol Appl Pharmacol. doi: Epub Dec 8. Quercetin reduces blood pressure in hypertensive subjects.
J Nutr. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebocontrolled cross-over study.
Br J Nutr. Epub Apr Flavonols and cardiovascular disease. Mol Aspects Med. Epub Sep The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets. Susan Di Santo. Question on dairy. Kefir grains prefer wholemilk. There are many reports of how it assists the growth of breast cancer cells, perhaps because of acidifying effect?
What is your opinion on kefir relative to bone health? Stacy Ann cargill. I have been recently diagnosed with weaken bones and multiply herniated disc. and I would love to get as many info as possible about this.
I take quercetin supplements but am not sure how much to take. Jesnette Howson. Vivian, How do you know if you are taking the right vitamins, and if you are taking too many or too little. What do you think about that. I Querxetin your program and your cook book, and we heaoth them.
Would appreciate your thoughts on the matter. I am presently taking garden of life calcium jealth consists mcha to increase bone density! Is it good? Thank you for the bone appetite cook book! joy markman. So my Prof. Vivian good luck to you — you are doing a great job.
Please answer me at my email address. I would be willing to stock your vitamins for South Africa if you would like. Thanks so much for being there. Best Joy Markman. Helen Kroll. Thanks, Helen. Customer Support. Thanks for your interest, Helen! hi vivian, thank you for your great health informations; they are very interesting and helpful.
I read them because i have the beginning of osteosporosis, and sometimes i feel Querceitn depressed. Have a great day, and hi to every one! My friend had your book which I was looking at. She told Qeurcetin that you have sales and sell books for half price that might be a little wrinkled.
Please let me know when the next time will be that you will do that again. Thank you very much, Roberta. I follow, mostly Dr. Early in Dec. last year, I broke both sides of my left ankle and discovered even worse Osteoporosis than I expected.
Joyce M. Supplement memory with Index Cards; Write SOBones foods on card with A for Acid;or B for base alkaline beside names ofFruit, Veggie, Nuts, Grains,etc— carry to store when shop each time.
Vivian Goldschmidt, MA. Regular yogurt has three times as much calcium than Greek yogurt and is therefore great for people who need more calcium in their diet. Greek yogurt has a lower potassium content than regular yogurt.
Every 6 oz serving of Greek yogurt contains around mg of potassium whereas regular yogurt contains around mg of potassium. How much quercetin does one need to take a day to obtain the benefits? Such as one or two apples a day or what amount of foods do you need to eat daily to get the benefit of quercetin?
Quercetin is a bioflavonoid common in the plant kingdom, especially high in onions, red wine, and green tea.
Ideally, we should be drinking 5 cups a day. Too many for me. JOYCE CORMACK.
: Quercetin and bone health| Frontiers | Pharmacological and mechanistic aspects of quercetin in osteoporosis | Hence, this work first discovered the impact of LP and quercetin in PMOP and confirmed that quercetin might be considered a novel PMOP treatment agent. This work discovered the mechanisms of LP on PMOP, the major constituents and downstream targets. LP constituent-target network revealed the foundation of LP. Flavonoids are the majority of the major constituents of LP. Besides, quercetin is a polyphenolic flavonoid that exerts anti-tumor activity, especially in traditional Chinese medicine [ 26 , 27 ]. In vitro studies have paid attention to chemopreventive activity and mechanisms underlying the function of quercetin in PMOP. In addition, p-AKT and p-PI3K are generally downregulated when osteoporosis occurs, illustrating that the progression of osteoporosis might be associated with cell injury [ 29 , 32 , 33 ]. JUN, FOS and TGF-β are key modulators in pyroptosis [ 34 , 35 ]. Meanwhile, these three proteins were also upregulated during the progression of osteoporosis [ 36 , 37 , 38 ]. Consistently, our work demonstrated that quercetin could abolish FAC-induced cell injury via the downregulation of JUN, FOS and TGF-β. Previous studies have shown that inhibition of FOS in Raw Further, we investigated its effect on MC3T3-E1 cells by overexpressing FOS. Quercetin significantly modulates osteoblast proliferation via FOS mediation. Some shortcomings existed in this work: the mechanisms underlying the impact of quercetin in PMOP remain further discovered. Thus, more detections are essential in the future. Thus, quercetin might act as a crucial agent for PMOP treatment. Yang Y, Miao L, Chang S, Zhang Q, Yu L, He P, Zhang Y, Fan W, Liu J, Hao X. Front Genet. Article CAS Google Scholar. Qian TY, Wan H, Huang CY, Hu XJ, Yao WF. Plasma LncRNA MALAT1 expressions are negatively associated with disease severity of postmenopausal osteoporosis. Lab Med. 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This work was supported by the Provincial Central Administration Project E and the Key Project of Hunan Provincial Department of Education 21A Department of Foot and Ankle Orthopedics, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China. Department of Extremities and Arthrosis, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China. Department of Pharmacy, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China. Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital of Central South University, No. You can also search for this author in PubMed Google Scholar. FZ contributed to conceptualization, methodology, writing—original draft preparation; WL contributed to software and validation; LW and BD contributed to data curation and Software; ZL and HW contributed to visualization and investigation; TD contributed to supervision, writing—reviewing and editing. All the authors above approved the version of the manuscript to be published. Correspondence to Ting Deng. The samples used in this research were approved by Animal Experimental Ethical Inspection in the Laboratory of The First Hospital of Hunan University of Chinese Medicine ZYFY Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Screening for quercetin concentrations. A CCK8 assay was used to detect the activity of MC3T3-E1 cells. B MC3T3-E1 cell apoptosis was assessed by flow cytometry. The effects of LP and quercetin on cell viability and apoptosis. A The viability of MC3T3-E1 cells was assessed by CCK8 assay. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Zhu, F. et al. Study on the treatment of postmenopausal osteoporosis with quercetin in Liuwei Dihuang Pill based on network pharmacology. J Orthop Surg Res 18 , 21 Download citation. Received : 22 September Accepted : 22 December Published : 09 January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Liuwei Dihuang Pill LP was verified to alleviate postmenopausal osteoporosis PMOP development. Methods Protein—protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. Results Quercetin was the major constituent of LP. Introduction Postmenopausal osteoporosis PMOP is a subtype of systemic metabolic bone disease, in which downregulated estrogen levels are a major cause [ 1 , 2 ]. Material and methods Exploration of LP component targets As mentioned above, the active constituents of LP were obtained: Fuling, Mudanpi, Jiuyurou, Shanyao, Shanzhuyu, Shudihuang and Zexie [ 14 ]. Manufacture of Venn diagrams The screened LP targets and PMOP targets were input into the Venn diagram creation software Venny 2. Topological analysis The PPI network was imported into Cytoscape 3. Molecular complex detection MCODE cluster analysis The PPI network was imported into Cytoscape 3. Gene Ontology GO analysis Common targets of LP and PMOP were subjected to GO enrichment pathway analysis using R4. Kyoto Encyclopedia of Genes and Genomes KEGG Traditionally, KEGG pathway analysis was one strategy for discovering biological functions and pathways. Preparation of LP medicated serum Five male SD rats of — g Hunan SJA Laboratory Animal Co. Cell culture and treatment Mouse osteoblasts MC3T3-E1 were bought from the ATCC USA. Alizarin red staining The osteogenic differentiation in cells was assessed by alizarin red staining. Western blot detection RIPA was applied to extract protein from cells. Flow cytometry Cells were trypsinized, washed and re-suspended in binding buffer. Statistical analysis SPSS v Full size image. Table 1 Ingredient list of Liuwei Dihuang Pills Full size table. Discussion According to Bayesian network meta-analysis, we found that corticosteroids, denosumab, Ibandronate, etc. Availability of data and materials The data used to support the findings of this study are included in the article. References Yang Y, Miao L, Chang S, Zhang Q, Yu L, He P, Zhang Y, Fan W, Liu J, Hao X. Article CAS Google Scholar Qian TY, Wan H, Huang CY, Hu XJ, Yao WF. Article Google Scholar Migliorini F, Maffulli N, Colarossi G, Eschweiler J, Tingart M, Betsch M. Article Google Scholar Migliorini F, Giorgino R, Hildebrand F, Spiezia F, Peretti GM, Alessandri-Bonetti M, Eschweiler J, Maffulli N. Article Google Scholar Gu H, Huang Z, Zhou K, Chen G, Bian C, Xu J, Yin X. Article Google Scholar Xu F, Gao F. Article CAS Google Scholar Ge JR, Xie LH, Chen J, Li SQ, Xu HJ, Lai YL, Qiu LL, Ni CB. Article Google Scholar Chen Q, Zhang Y, Meng Q, Wang S, Yu X, Cai D, Cheng P, Li Y, Bian H. Article CAS Google Scholar Zhang K, Weng H, Yang J, Wu C. 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Mol Pharmacol — Download references. This work was supported by grants to H. Yamamoto, Y. Taketani and E. Takeda from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by grants from the 21st Century COE Program, Human Nutritional Science on Stress Control, Tokushima, Japan; and by Biogenics Research, Kagome Co. The authors thank Mr. Nonaka Elk Corporation and Mr. Hayashi Kagome , for valuable discussions and technical support during this research. We gratefully acknowledge the assistance of our laboratory colleagues. Department of Clinical Nutrition, Institute of Health Biosciences, The University of Tokushima, Kuramoto, Tokushima, , Japan. Department of Food Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Institute of Molecular and Cellular Biosciences, The University of Tokyo Graduate School, Tokyo, Japan. Biogenics Research, Kagome Co. You can also search for this author in PubMed Google Scholar. Correspondence to Hironori Yamamoto. Tsuji, M. et al. |
| Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence | Biofactors — Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. Wattel A, Kamel S, Prouillet C, Petit JP, Lorget F, Offord E, Brazier M Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP J Cell Biochem — Yoshizumi M, Tsuchiya K, Suzaki Y, Kirima K, Kyaw M, Moon J-H, Terao J, Tamaki T Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1signaling pathway. Asagiri M, Takayanagi H The molecular understanding of osteoclast differentiation. Kawai Y, Nishikawa T, Shiba Y, Saito S, Murota K, Shibata N, Kobayashi M, Kanayama M, Uchida K, Terao J Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. Prouillet C, Mazière JC, Mazière C, Wattel A, Brazier M, Kamel S Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG human osteoblasts through ERK and estrogen receptor pathway. Notoya M, Tsukamoto Y, Nishimura H, Woo JT, Nagai K, Lee IS, Hagiwara H Quercetin, a flavonoid, inhibits the proliferation, differentiation, and mineralization of osteoblasts in vitro. Eur J Pharmacol — Son YO, Kook SH, Choi KC, Jang YS, Jeon YM, Kim JG, Lee KY, Kim J, Chung MS, Chung GH, Lee JC Quercetin, a bioflavonoid, accelerates TNF-alpha-induced growth inhibition and apoptosis in MC3T3-E1 osteoblastic cells. Kim DS, Takai H, Arai M, Araki S, Mezawa M, Kawai Y, Murota K, Terao J, Ogata Y Effects of quercetin and quercetin 3-glucuronide on the expression of bone sialoprotein gene. Wuttke W, Jarry H, Westphalen S, Christoffel V, Seidlová-Wuttke D Phytoestrogens for hormone replacement therapy? J Steroid Biochem Mol Biol — Maggiolini M, Bonofiglio D, Marsico S, Panno ML, Cenni B, Picard D, Andò S Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol — Download references. This work was supported by grants to H. Yamamoto, Y. Taketani and E. Takeda from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by grants from the 21st Century COE Program, Human Nutritional Science on Stress Control, Tokushima, Japan; and by Biogenics Research, Kagome Co. The authors thank Mr. Nonaka Elk Corporation and Mr. Hayashi Kagome , for valuable discussions and technical support during this research. We gratefully acknowledge the assistance of our laboratory colleagues. Department of Clinical Nutrition, Institute of Health Biosciences, The University of Tokushima, Kuramoto, Tokushima, , Japan. Department of Food Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Institute of Molecular and Cellular Biosciences, The University of Tokyo Graduate School, Tokyo, Japan. Biogenics Research, Kagome Co. You can also search for this author in PubMed Google Scholar. Correspondence to Hironori Yamamoto. Tsuji, M. et al. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice. J Bone Miner Metab 27 , — Download citation. Received : 19 November Accepted : 30 March Published : 04 June Issue Date : November Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Abstract Quercetin is a major dietary flavonoid found in onions and other vegetables, and potentially has beneficial effects on disease prevention. Access this article Log in via an institution. References Horowitz MC, Xi Y, Wilson K, Kacena MA Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev —18 Article CAS PubMed Google Scholar Gallagher JC Estrogen: prevention and treatment of osteoporosis. San Diego, CA, pp — Google Scholar Melton LJ Epidemiology of fractures. 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A flow cytometer was then used to detect the generation of reactive oxygen species. The cells were resuspended in PBS and subjected to flow cytometric analysis. The test was performed with a FACS Calibur flow cytometer BD Biosciences , and the data were analyzed by FlowJo software Treestar, Ashland, OR, USA. Statistical analyses were carried out using GraphPad Prism 8. Statistical analysis was performed in all groups by one-way ANOVA. MicroCT analysis showed that HLS caused severe damage to the cancellous bone and cortical bone of mice. Treatment of HLS mice with high doses of Quer reversed the changes in bone microstructure caused by unloading. Representative pictures of the cancellous bone of mice in each group are shown. In contrast, the SMI and Tb. N, and Tb. Representative pictures of the cortical bone of mice in each group are shown in Fig. Representative μCT images of trabecular bones of distal femurs a and cortical bone of diaphyseal femurs b from male mice subjected to hindlimb suspension HLS for 4 weeks or ground control mice CON that were sacrificed at 13 weeks of age. N , trabecular spacing Tb. Sp , trabecular thickness Tb. Th , structural model index SMI , and bone mineral density BMD in trabecular bone. d Analysis of the total volume, cortical volume, and cortical thickness in cortical bone. There was no difference in P1NP levels between HLS and CON mice. CON represents the ground control group. a CTX1, b TRACP5b, and c P1NP. The results of the three-point bending experiment showed that there was no significant difference in the femoral biomechanical parameters of each group after hindlimb unloading. To determine whether Quer could affect bone surface remodeling and histomorphometry, TRAP staining of osteoclasts in the trabecular bone and cortical bone of the distal femur was performed Fig. Figure 5e shows a photograph of a tibial specimen with fluorescence double labeling. Representative images of TRAP-positive red osteoclasts in trabecular bones of distal femurs a and cortical bone of diaphyseal femurs b. a Representative images of TRAP-positive osteoclasts. b The dose-dependent inhibitory effects of Quer on RANKL-induced osteoclastogenesis were evaluated by ImageJ analysis. c Cluster analysis of differentially expressed genes was performed with RNA-Seq. d, e Based on the enrichment analysis of GO function and KEGG pathways for the DEGs, eight genes related to osteoclast differentiation, osteoclast fusion, bone resorption, and bone development d were selected and verified by qPCR e. RNA-seq of osteoclasts induced to differentiate by RANKL was performed to observe the DEGs related to the inhibition of osteoclast formation by Quer. Based on the enrichment analysis of GO function and KEGG pathways performed for the DEGs, eight genes related to osteoclast differentiation, osteoclast fusion, bone resorption, and bone development were selected and verified by qPCR Fig. The effect of Quer on STC1 expression in the Con siRNA and STC1 siRNA groups was measured by qPCR a and Western blotting b. The effect of Quer on ROS production in the Con siRNA and STC1 siRNA groups was measured by flow cytometry d. Quantification of the osteoclast area is shown in the bar graphs g. h , i IL-6 and TNF-α expression levels were induced by LPS in the supernatant of RANKL-induced osteoclasts. j Quer prevented LPS-induced STC1 reduction. k Quer inhibited the expression of p-JNK and p-NF-κB. The effect of Quer on reducing the expression of p-JNK and p-NF-κB was weakened by STC1 siRNA. IL-6 and TNF-α expression levels were induced by LPS in the supernatant of RANKL-induced osteoclasts. Quer prevented an LPS-induced reduction in STC1 expression Fig. In addition, Quer obviously inhibited the expression of p-JNK and p-NF-κB. The reduction of p-JNK and p-NF-κB expression by Quer was blocked by STC1 siRNA Fig. We detected the expression of STC1, NFATc1, and Ctsk in osteoclasts induced to differentiate from primary bone marrow cells in each group of mice by qPCR. The results showed that Quer increased the expression of STC1 Fig. Primary bone marrow cells were induced to differentiate into TRAP-positive osteoclasts. a — c , Quer increased the mRNA expression of STC1 a and reduced the mRNA expression of Ctsk b and NFATc1 c mRNA in primary osteoclasts. d , e siSTC1 reduced the inhibitory effect of Quer on osteoclastogenesis in primary osteoclasts d. Quantification of the osteoclast area is shown in the bar graphs e. Prolonged bed rest, disuse, and spaceflight induce disuse bone osteoporosis by damaging the bone microstructure and reducing bone volume. Only 1 month of spaceflight can reduce BMD by ~1. However, the pathology of disuse osteoporosis is still unclear and needs to be clarified for the development of effective countermeasures. A growing number of studies have shown that the intake of flavonoids via the diet is closely related to the reduction of osteoporosis risk [ 29 ]. Quer, as a major dietary flavonoid, has aroused our interest for the prevention of osteoporosis. Previous studies on the effects of Quer on osteoporosis in vivo mainly focused on osteoporosis induced by ovariectomy, while our study investigated the pharmacological inhibitory effects and mechanism of Quer in disuse osteoporosis induced by hindlimb unloading in mice. Our findings showed that Quer at a high dose had obvious bone protective effects. It reduced bone loss in mice subjected to long-term hindlimb unloading by inhibiting bone resorption and effectively increasing bone formation. N in cancellous bone and the increase in Tb. Sp and SMI. Neither unloading nor Quer had an effect on Tb. Th in trabecular bone, the total volume of cortical bone, the cortical volume, and the cortical thickness in mice. The results of the static index of bone histomorphometry demonstrated that administration of Quer improved the endosteal N. Neither hindlimb unloading nor Quer had an effect on the endosteal N. Further examination of serum bone turnover markers revealed that the level of CTX1, a marker related to bone resorption, was decreased after hindlimb unloading, but the level of TRACP5b, another marker related to bone resorption, did not change. Quer reduced CTX1 and TRACP5b levels compared with those in the HLS group. The level of P1NP, a marker associated with bone formation, did not change after hindlimb unloading. However, Quer at both the middle and high dose increased the level of P1NP compared with that in the HLS group. All the above results indicate that Quer has the dual effects of promoting bone formation and inhibiting bone resorption, which contributes to resistance to disuse-induced bone loss. At present, studies of the anti-osteoporotic effects and mechanisms of Quer are mainly focused on bone formation. However, our results suggest that Quer has obvious inhibitory effects on osteoclasts. For example, Quer can increase the N. In our study, the RNA-Seq transcription analysis of Quer-treated osteoclasts induced by RANKL was performed to reveal the function of Quer in osteoclasts. RNA-seq analysis identified DEGs in Quer-treated cells, including upregulated genes and downregulated genes. Based on the enrichment analysis of GO function and KEGG pathways for the DEGs, eight genes related to osteoclast differentiation, osteoclast fusion, bone resorption, and bone development were selected and verified by qPCR. Quer can upregulate STC1 and SCOCS3 gene expression and reduce Itgb3, Jun, Vegfa, Tsc22d3, Itgbr1, and Cd gene expression. Previous reports have shown that flavonoids can act as antioxidants to scavenge ROS [ 13 , 30 , 31 , 32 ]. A growing number of studies have demonstrated that ROS may be the main cause of osteoporosis and that its contribution to oxidative stress plays an important role in osteoporosis [ 33 , 34 ]. Our findings indicate that Quer can reduce the generation of ROS during RANKL-induced osteoclastogenesis. We found that the antioxidant hormone STC1 was highly expressed in the Quer group based on the gene expression data. STC1 is highly expressed in muscle and bone tissue during embryonic development and is mainly associated with osteoblast differentiation and cartilage growth inhibition [ 36 , 37 ]. This is the first study to show that STC1 can play a role in RANKL-induced osteoclastogenesis. In addition, STC1 was knocked down in RAW The results demonstrated that STC1 knockdown can improve ROS production during RANKL-induced osteoclastogenesis. TRAP staining analysis has shown that STC1 knockdown can promote osteoclastogenesis and that the inhibitory effect of Quer on osteoclastogenesis was blocked by siSTC1. In addition, it was confirmed that siSTC1 could reverse the inhibition of osteoclast formation by Quer ex vivo. These findings suggest that STC1 plays an important role in inducing osteoclastogenesis in vitro and in vivo. Furthermore, we found that Quer inhibited the expression of TNF-α and IL-6, which are upstream molecules of STC1, and suppressed the activation of JNK and NF-κB, which are downstream molecules of ROS. Furthermore, we further observed the expression of STC1, NFATc1, and Ctsk mRNA during osteoclastogenesis by isolating bone marrow cells from the HLS model mice in each group. The findings have shown that Quer can increase the expression of STC1 and inhibit the expression of NFATc1 and Ctsk. NFATc1 integrates RANKL signaling to mediate the terminal differentiation of osteoclasts during HLS, resulting in bone loss in mice [ 38 ]. Ctsk is a cysteine protease secreted by osteoclasts and is essential for the degradation of matrix collagen during bone resorption [ 39 ]. The decrease in NFATc1 and Ctsk mRNA expression in the Quer group is consistent with the findings of tissue morphology, cell culture, and bone metabolism markers. Taken together, the results indicate that Quer can promote STC1 expression and play a dual role in inhibiting bone resorption. This study has some limitations. Although Quer can obviously inhibit bone resorption, the molecular mechanism of Quer, the regulation of related proteins, and the role of the target genes identified based on the RNA-seq results require systematic exploration. In addition, our finding that Quer has no effects on a bone formation-related indicator, endocortical N. Therefore, we will thoroughly explore the mechanism of Quer involved in promoting bone formation in hindlimb unloading mice in future research. In conclusion, Quer can reduce bone loss induced by unloading in mice and protect bones, which can be achieved by STC1-mediated inhibition of osteoclastogenesis. Our findings suggest that Quer as an alternative supplement can be used to prevent and treat bone loss caused by unloading. Lam H, Qin Y. 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