Abstract
Background
Postmenopausal osteoporosis and osteoporotic fractures constitute an increasing problem in developing countries. Kaempferol, isolated from seeds of Cuscuta chinensis, is an active flavonoid inhibiting in vitro osteoclast activity. The aim of the presented research was an assessment of kaempferol effect on estrogen-deficiency-induced bone structure disturbances in rats.
Methods
The study was performed on 24 Wistar female rats divided into 3 groups: SHAM — rats undergoing a “sham” surgery, OVX-C — control group of animals that underwent ovariectomy, OVX-K — rats undergoing ovariectomy and receiving kaempferol for 8 weeks (from day 56 to day 112).
Results
In the OVX-K group, contrary to the OVX-C one, there was no significant decrease in femoral bone mineral density (BMD). A significant increase in Young’s modulus was observed in the OVX-K group compared to the OVX-C (15.33 ± 2.51 GPa vs. 11.14 ± 1.93 GPa, p < 0.05). A decreased bone turnover was detected in the OVX-K group. Tissue volume ratio (BV/TV) and trabecular bone perimeter were increased in the OVX-K group compared to the OVX-C one (0.241 ± 0.037 vs. 0.170 ± 0.022, p < 0.05 and 15.52 ± 2.78 mm vs. 9.67 ± 3.07 mm, p < 0.05, respectively).
Conclusion
Kaempferol has a beneficial influence on estrogen-deficiency-induced disturbances of bone structure in rats.
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References
Khajuria DK, Razdan R, Mahapatra DR. Drugs for the management of osteoporosis: a review. Rev Bras Reumatol 2011;51(4):365–82.
Puszczewicz M. Rheumatology great internal medicine. Medical Tribune Polska; 2011 [in polish].
van Staa TP, Geusens P, Bijlsma JWJ, Leufkens HGM, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006;54(10):3104–12.
Becker DJ, Kilgore ML, Morrisey MA. The societal burden of osteoporosis. Curr Rheumatol Rep 2010;12(3):186–91.
Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, Giannini S, et al. Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo 2016;68(1):1–39.
McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 2013;126(1):13–20.
Bejhed RS, Kharazmi M, Hallberg P. Identification of risk factors for bisphosphonate-associated atypical femoral fractures and osteonecrosis of the jaw in a pharmacovigilance database. Ann Pharmacother 2016;50(8):616–24.
Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CYC. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90(3):1294–301.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA 2002;288(3):321–33.
Lewiecki EM, Miller PD, Harris ST, Bauer DC, Davison KS, Dian L, et al. Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis. J Clin Densitom 2014;17(4):490–5.
Donnapee S, Li J, Yang X, Ge A, Donkor PO, Gao X, et al. Cuscuta chinensis lam.: a systematic review on ethnopharmacology, phytochemistry and pharmacology of an important traditional herbal medicine. J Ethnopharmacol 2014;157:292–308.
Yang L, Chen Q, Wang F, Zhang G. Antiosteoporotic compounds from seeds of cuscuta chinensis. J Ethnopharmacol 2011;135(2):553–60.
Trivedi R, Kumar A, Gupta V, Kumar S, Nagar GK, Romero JR, et al. Effects of egb 761 on bone mineral density, bone microstructure, and osteoblast function: possible roles of quercetin and kaempferol. Mol Cell Endocrinol 2009;302(1):86–91.
Wang J, Fang F, Huang Z, Wang Y, Wong C. Kaempferol is an estrogen-related receptor alpha and gamma inverse agonist. FEBS Lett 2009;583(4):643–7.
Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit J, et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol 2003;65(1):35–42.
Trivedi R, Kumar S, Kumar A, Siddiqui JA, Swarnkar G, Gupta V, et al. Kaempferol has osteogenic effect in ovariectomized adult sprague-dawley rats. Mol Cell Endocrinol 2008;289(1–2):85–93.
Nowak B, Matuszewska A, Filipiak J, Nikodem A, Merwid-Ląd A, Piesniewska M, et al. The influence of bexarotene, a selective agonist of the retinoid receptor x (rxr), and tazarotene, a selective agonist of the retinoid acid receptor (rar), on bone metabolism in rats. Adv Med Sci 2016;61(1):85–9.
Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, et al. Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the asbmr histomorphometry nomenclature committee. J Bone Miner Res 2013;28(1):2–17.
Lee W, Lee E, Sung M, Yoo W. Kaempferol inhibits IL-1β-stimulated, rankl-mediated osteoclastogenesis via downregulation of mapks, c-fos, and nfatc1. Inflammation 2014;37(4):1221–30.
Pang JL, Ricupero DA, Huang S, Fatma N, Singh DP, Romero JR, et al. Differential activity of kaempferol and quercetin in attenuating tumor necrosis factor receptor family signaling in bone cells. Biochem Pharmacol 2006;71(6):818–26.
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93(2):165–76.
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361(8):756–65.
Prouillet C, Mazière J, Mazière C, Wattel A, Brazier M, Kamel S. Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in mg-63 human osteoblasts through erk and estrogen receptor pathway. Biochem Pharmacol 2004;67(7):1307–13.
Taku K, Melby MK, Kurzer MS, Mizuno S, Watanabe S, Ishimi Y. Effects of soy isoflavone supplements on bone turnover markers in menopausal women: systematic review and meta-analysis of randomized controlled trials. Bone 2010;47(2):413–23.
Sathyapalan T, Aye M, Rigby AS, Fraser WD, Thatcher NJ, Kilpatrick ES, et al. Soy reduces bone turnover markers in women during early menopause-a randomized controlled trial. J Bone Miner Res 2016, doi:http://dx.doi.org/10.1002/jbmr.2927 [Epub ahead of print].
Fonseca D, Ward WE. Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice. Bone 2004;35(2):489–97.
Fu S, Zeng G, Zong S, Zhang Z, Zou B, Fang Y, et al. Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats. Nutr Res 2014;34(6):467–77.
Li Q, Hu B, Huang L, Chen Y, Weng L, Zheng H, et al. Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus in ovariectomized rats. Acta Pharmacol Sin 2003;24(6):599–604.
Dai R, Ma Y, Sheng Z, Jin Y, Zhang Y, Fang L, et al. Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats. J Bone Miner Metab 2008;26(4):342–9.
Hooshmand S, Juma S, Arjmandi BH. Combination of genistin and fructooligosaccharides prevents bone loss in ovarian hormone deficiency. J Med Food 2010;13(2):320–5.
Toh MF, Mendonca E, Eddie SL, Endsley MP, Lantvit DD, Petukhov PA, et al. Kaempferol exhibits progestogenic effects in ovariectomized rats. J Steroids Horm Sci 2014;5(3):136.
Kim S, Hwang K, Choi K. Treatment with kaempferol suppresses breast cancer cell growth caused by estrogen and triclosan in cellular and xenograft breast cancer models. J Nutr Biochem 2016;28:70–82.
Francisco AMC, Carbonel AF, Simões RS, Soares JMJ, Baracat EC, Haidar MA. Do extracts of oral soybean augment the trophic effect of estrogen on the rat uterus? Climacteric 2013;16(1):161–8.
Michelin RM, Al-Nakkash L, Broderick TL, Plochocki JH. Genistein treatment increases bone mass in obese, hyperglycemic mice. Diabetes Metab Syndr Obes 2016;9:63–70.
Kim H, Nelson-Dooley C, Della-Fera MA, Yang J, Zhang W, Duan J, et al. Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 2006;136(2):409–14.
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Nowak, B., Matuszewska, A., Nikodem, A. et al. Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia. Pharmacol. Rep 69, 1113–1119 (2017). https://doi.org/10.1016/j.pharep.2017.05.002
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DOI: https://doi.org/10.1016/j.pharep.2017.05.002