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A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone

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Abstract

Summary

The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG.

Introduction

Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3′,4′,5,7-Pentahydroxyflavone-6-C-β-d-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function.

Methods

Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0 mg kg−1 day−1) orally for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography.

Results

QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels.

Conclusion

QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.

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Acknowledgments

This study was supported by grant from the Ministry of Health and Family Welfare, Government of India. Funding from the Indian Council of Medical Research, Government of India (N.C.) is acknowledged. Research fellowship grants from University Grants Commission (J.A.S., A.K.G.), Department of Biotechnology (K.S.), and Council of Scientific and Industrial Research (G.S., B.C.,P.R, M.K.,V.G.,L.M.), Government of India, are also acknowledged.

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Authors and Affiliations

  1. Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India

    J. A. Siddiqui, G. Swarnkar, K. Sharan, B. Chakravarti, A. K. Gautam & N. Chattopadhyay

  2. Division of Medicinal & Process Chemistry, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India

    P. Rawat, M. Kumar & R. Maurya

  3. Division of Pharmaceutics, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India

    V. Gupta & A. K. Dwivedi

  4. Division of Pharmacokinetics and Metabolism, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India

    L. Manickavasagam

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  1. J. A. Siddiqui
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  2. G. Swarnkar
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  3. K. Sharan
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  9. L. Manickavasagam
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  11. R. Maurya
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  12. N. Chattopadhyay
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Corresponding author

Correspondence to N. Chattopadhyay.

Additional information

J. A. Siddiqui and G. Swarnkar contributed equally to this study.

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Supplementary Fig. 1

There were no significant changes in the initial and final body weights among the vehicle and QCG-treated groups (DOC 25 kb)

Supplementary Fig. 2

QCG treatment to OVx rats had no significant effect on gain of body weight due to OVx when compared with OVx + vehicle group. *P < 0.05 compared to OVx+vehicle-treated group (DOC 25 kb)

Supplementary Fig. 3

Representative μCT images of the entire cross section of the femur epiphysis. Representative μCT images of the entire cross section of the tibia proximal (DOC 1408 kb)

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Siddiqui, J.A., Swarnkar, G., Sharan, K. et al. A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone. Osteoporos Int 22, 3013–3027 (2011). https://doi.org/10.1007/s00198-010-1519-4

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