Abstract
Objective
To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice.
Methods
In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed.
Results
Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05).
Conclusion
HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Li Y, Lu SS, Tang GY, Hou M, Tang Q, Zhang XN, et al. Effect of Morinda officinalis Capsule on osteoporosis in ovariectomized rats. Chin J Nat Med 2014;12:204–212.
Ishikawa K, Nagai T, Sakamoto K, Ohara K, Eguro T, Ito H, et al. High bone turnover elevates the risk of denosumabinduced hypocalcemia in women with postmenopausal osteoporosis. Ther Clin Risk Manag 2016;12:1831–1840.
Reid IR. Osteoporosis: non-HRT treatments. Rev Gynaecol Pract 2002;2:48–53.
Aghamiri V, Mirghafourvand M, Mohammad-Alizadeh-Charandabi S, Nazemiyeh H. The effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot flashes: a randomized placebo-controlled trial. Complement Ther Clin Pract 2016;23:130–135.
Takahashi K, Osada K. Effect of dietary purified xanthohumol from hop (Humulus lupulus L.) pomace on adipose tissue mass, fasting blood glucose level, and lipid metabolism in KK-Ay mice. J Oleo Sci 2017;66:531–541.
Morimoto-Kobayashi Y, Ohara K, Ashigai H, Kanaya T, Koizumi K, Manabe F, et al. Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study. Nutr J 2016;15:25–37.
Liu M, Yin H, Qian XK, Dong JJ, Qian ZH, Miao JL. Xanthohumol, a prenylated chalcone from hops, inhibits the viability and stemness of doxorubicin-resistant MCF-7/ADR cells. Molecules 2016;22:36–48.
Li J, Zeng L, Xie J, Yue ZY, Deng HY, Ma XY, et al. Inhibition of osteoclastogenesis and bone resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops. Sci Rep 2015;5:17605.
Jeong HM, Han EH, Jin YH, Choi YH, Lee KY, Jeong HG. Biochemical and biophysical research communications xanthohumol from the hop plant stimulates osteoblast differentiation by RUNX2 activation. Biochem Biophys Res Commun 2011;409:82–89.
Heyerick A, Vervarcke S, Depypere H, Bracke M, Keukeleire DD. A first prospective, randomized, doubleblind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas 2006;54:164–175.
Keiler AM, Zierau O, Kretzschmar G. Hop extracts and hop substances in treatment of menopausal complaints. Planta Med 2013;79:576–579.
Zhang ZG, Zhang QY, Yang H, Liu W, Zhang ND, Qin LP, et al. Monotropein isolated from the roots of Morinda officinalis increases osteoblastic bone formation and prevents bone loss in ovariectomized mice. Fitoterapia 2016;110:166–172.
Gu G, Hentunen TA, Nars M, Härkönen PL, Väänänen HK. Estrogen protects primary osteocytes against glucocorticoidinduced apoptosis. Apoptosis 2005;10:583–595.
Bao LL, Qin LP, Liu L, Wu YB, Han T, Xue LM, et al. Anthraquinone compounds from Morinda officinalis inhibit osteoclastic bone resorption in vitro. Chem Biol Interact 2011;194:97–105.
Carson JA, Manolagas SC. Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease. Bone 2015;80:67–78.
Cos P, De Bruyne T, Apers S, Vanden Berghe D, Pieters L, Vlietinck AJ. Phytoestrogens: recent developments. Planta Med 2003;69:589–599.
Levin VA, Jiang X, Kagan R. Estrogen therapy for osteoporosis in the modern era. Osteoporos Int 2018;29:1049–1055.
Overk CR, Guo J, Chadwick LR, Lantvit DD, Minassi A, Appendino G, et al. In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact 2008;176:30–39.
Gallagher JC, Tella SH. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol 2014;142:155–170.
You L, Sheng ZY, Tang CL, Chen L, Pan L, Chen JY. High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats. Acta Pharmacol Sin 2011;32:1498–1504.
Tolba MF, El-Serafi AT, Omar HA. Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo: Impact on oxidative stress and RANKL/OPG signals. Toxicol Appl Pharmacol 2017;324:26–35.
Holick MF, Lamb JJ, Lerman RH, Konda VR, Darland G, Minich DM, et al. Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial. J Bone Miner Metab 2010;28:342–350.
Chan GK, Duque G. Age-related bone loss: old bone, new facts. Gerontology 2002;48:62–71.
Wang C, Meng MX, Tang XL, Chen KM, Zhang L, Liu WN, et al. The proliferation, differentiation, and mineralization effects of puerarin on osteoblasts in vitro. Chin J Nat Med 2014;12:436–442.
Neve A, Corrado A, Cantatore FP. Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 2011;343:289–302.
Walia B, Lingenheld E, Duong L, Sanjay A, Drissi H. A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair. Ann N Y Acad Sci 2018;1415:57–68.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337–342.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the National Natural Science Foundation of China (No. U1603283)
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Xia, Ts., Lin, Ly., Zhang, Qy. et al. Humulus lupulus L. Extract Prevents Ovariectomy-Induced Osteoporosis in Mice and Regulates Activities of Osteoblasts and Osteoclasts. Chin. J. Integr. Med. 27, 31–38 (2021). https://doi.org/10.1007/s11655-019-2700-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-019-2700-z