Dried root of Rehmannia glutinosa prevents bone loss in ovariectomized rats

Dong Wook Lim, Yun Tai Kim, Dong Wook Lim, Yun Tai Kim

Abstract

Dried root of Rehmannia glutinosa is a kidney-tonifying herbal medicine with a long history of safe use in traditional folk medicine for the treatment of joint diseases. This study was conducted to investigate prevention of bone loss by a standardized dried root of R. glutinosa in an ovariectomized (OVX) rat model of osteoporosis. The OVX groups were divided into five groups treated with distilled water, 17β-estradiol (E2 10 µg/kg, once daily, i.p) and dried root of R. glutinosa extracts (DRGE 30, 100, and 300 mg/kg, twice daily, p.o) for eight weeks. We measured the body, organs, and uterus weights, and femur and lumbar vertebrae bone mineral density (BMD), serum alkaline phosphatase (ALP), estradiol levels. The treatments with DRGE 300 mg/kg significantly inhibited BMD decrease in the femur and lumbar (17.5% and 16.4%, p < 0.05, respectively) by OVX without affecting the body, organs, and uterus weights. Also, serum ALP level in the DRGE 300 mg/kg treated group was significantly decreased, but the estradiol level did not change in serum of the DRGE 300 mg/kg treated group. These results show that DRGE is able to prevent OVX-induced bone loss without influencing hormones such as estrogen.

Figures

Figure 1
Figure 1
2-D HPLC chromatograms for standardization of DRGE.
Figure 2
Figure 2
(A) Effects of DRGE on BMD in right femur and (B) lumbar vertebrae (g/cm2) of OVX rats by dual energy X-ray absorptiometry (DXA). These BMD values were determined weekly during the experimental period. Data are mean ± SD values (n = 12 per group). * p < 0.05, ** p < 0.01, significantly difference from the OVX-control group.
Figure 3
Figure 3
(A) Effects of DRGE on body weight gain and (B) body weight (g) in OVX rats. The body weight was recorded weekly during the experimental period. The body weight gain was calculated by the equation: final body weight - initial body weight. Data are mean ± SD values (n = 12 per group). * p < 0.05, significantly difference from the OVX-control group.
Figure 4
Figure 4
(A) Effects of DRGE on change in uterus and (B) organ index (mg/g). Uterus and organs were dissected, washed with saline, and immediately weight for analysis. Data are mean ± SD values (n = 12 per group). * p < 0.05, significantly difference from the OVX-control group.
Figure 5
Figure 5
(A) Effects of DRGE on ALP and (B) estradiol concentrations in OVX rat. At the end of the treatment period, blood sample was collected via abdominal aorta. Serum ALP and estradiol were measured by biochemical analyzer. Data are mean ± SD values (n = 12 per group). ** p < 0.01, ** p < 0.001, significantly difference from the OVX-control group.

References

    1. Raisz L.G. Pathogenesis of osteoporosis: Concepts, conflicts, and prospects. J. Clin. Invest. 2005;115:3318–3325. doi: 10.1172/JCI27071.
    1. Hansen M.A., Overgaard K., Riis B.J., Christiansen C. Potential risk factors for development of postmenopausal osteoporosis--examined over a 12-year period. Osteoporos. Int. 1991;1:95–102.
    1. Riggs B.L., Khosla S., Melton L.J., 3rd A unitary model for involutional osteoporosis: Estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J. Bone Miner. Res. 1998;13:763–773. doi: 10.1359/jbmr.1998.13.5.763. 3rd.
    1. Nelson H.D., Humphrey L.L., Nygren P., Teutsch S.M., Allan J.D. Postmenopausal hormone replacement therapy: Scientific review. JAMA. 2002;288:872–881. doi: 10.1001/jama.288.7.872.
    1. Pradhan A.D., Manson J.E., Rossouw J.E., Siscovick D.S., Mouton C.P., Rifai N., Wallace R.B., Jackson R.D., Pettinger M.B., Ridker P.M. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: Prospective analysis from the Women’s Health Initiative observational study. JAMA. 2002;288:980–987. doi: 10.1001/jama.288.8.980.
    1. Chang W.T., Choi Y.H., van der Heijden R., Lee M.S., Lin M.K., Kong H., Kim H.K., Verpoorte R., Hankemeier T., van der Greef J., et al. Traditional processing strongly affects metabolite composition by hydrolysis in Rehmannia glutinosa roots. Chem. Pharm. Bull. 2011;59:546–552. doi: 10.1248/cpb.59.546.
    1. Zhang R.X., Li M.X., Jia Z.P. Rehmannia glutinosa: Review of botany, chemistry and pharmacology. J. Ethnopharmacol. 2008;117:199–214. doi: 10.1016/j.jep.2008.02.018.
    1. Chao J.C., Chiang S.W., Wang C.C., Tsai Y.H., Wu M.S. Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J. Gastroenterol. 2006;12:4478–4484.
    1. Zhang D., Wen X.S., Wang X.Y., Shi M., Zhao Y. Antidepressant effect of Shudihuang on mice exposed to unpredictable chronic mild stress. J. Ethnopharmacol. 2009;123:55–60. doi: 10.1016/j.jep.2009.02.029.
    1. Chang G.T., Min S.Y., Kim J.H., Kim S.H., Kim J.K., Kim C.H. Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs. Vascul. Pharmacol. 2005;43:283–288. doi: 10.1016/j.vph.2005.08.014.
    1. Kiho T., Watanabe T., Nagai K., Ukai S. Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver. Yakugaku zasshi. 1992;112:393–400.
    1. Oh K.O., Kim S.W., Kim J.Y., Ko S.Y., Kim H.M., Baek J.H., Ryoo H.M., Kim J.K. Effect of Rehmannia glutinosa Libosch extracts on bone metabolism. Clinica Chimica Acta. 2003;334:185–195. doi: 10.1016/S0009-8981(03)00238-9.
    1. Jin U.H., Kim D.I., Lee T.K., Lee D.N., Kim J.K., Lee I.S., Kim C.H. Herbal formulation, Yukmi-jihang-tang-Jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression. J. Ethnopharmacol. 2006;106:333–343. doi: 10.1016/j.jep.2006.01.012.
    1. Liu H.D., Lin F.S., Li E., Wu M.S., Tong X.X. The influence of the different components of nourishing kidney herbs on osteoporosis rats. Zhongguo Zhongyao Zazhi. 2003;28:262–265.
    1. Chang W.T., Thissen U., Ehlert K.A., Koek M.M., Jellema R.H., Hankemeier T., van der Greef J., Wang M. Effects of growth conditions and processing on Rehmannia glutinosa using fingerprint strategy. Planta medica. 2006;72:458–467. doi: 10.1055/s-2005-916241.
    1. Hoegh-Andersen P., Tanko L.B., Andersen T.L., Lundberg C.V., Mo J.A., Heegaard A.M., Delaisse J.M., Christgau S. Ovariectomized rats as a model of postmenopausal osteoarthritis: Validation and application. Arthritis Res. Ther. 2004;6:R169–R180. doi: 10.1186/ar1152.
    1. Jee W.S., Yao W. Overview: Animal models of osteopenia and osteoporosis. J. Musculoskelet. Neuronal Interact. 2001;1:193–207.
    1. Lelovas P.P., Xanthos T.T., Thoma S.E., Lyritis G.P., Dontas I.A. The laboratory rat as an animal model for osteoporosis research. Comp. Med. 2008;58:424–430.
    1. Nishizawa Y., Nakamura T., Ohta H., Kushida K., Gorai I., Shiraki M., Fukunaga M., Hosoi T., Miki T., Chaki O., et al. Guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004) J. Bone Miner. Metab. 2005;23:97–104.
    1. Yogesh H.S., Chandrashekhar V.M., Katti H.R., Ganapaty S., Raghavendra H.L., Gowda G.K., Goplakhrishna B. Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats. J. Ethnopharmacol. 2011;134:334–338. doi: 10.1016/j.jep.2010.12.013.
    1. Devareddy L., Khalil D.A., Smith B.J., Lucas E.A., Soung D.Y., Marlow D.D., Arjmandi B.H. Soy moderately improves microstructural properties without affecting bone mass in an ovariectomized rat model of osteoporosis. Bone. 2006;38:686–693. doi: 10.1016/j.bone.2005.10.024.
    1. Dang Z.C., Van Bezooijen R.L., Karperien M., Papapoulos S.E., Lowik C.W.G.M. Exposure of KS483 cells to estrogen enhances osteogenesis and inhibits adipogenesis. J. Bone Miner. Res. 2002;17:394–405. doi: 10.1359/jbmr.2002.17.3.394.
    1. Heine P.A., Taylor J.A., Iwamoto G.A., Lubahn D.B., Cooke P.S. Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc. Natl. Acad. Sci. USA. 2000;97:12729–12734.
    1. Joyner J.M., Hutley L.J., Cameron D.P. Estrogen receptors in human preadipocytes. Endocrine. 2001;15:225–230. doi: 10.1385/ENDO:15:2:225.
    1. Hewitt S.C., Korach K.S. Oestrogen receptor knockout mice: Roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction. 2003;125:143–149. doi: 10.1530/rep.0.1250143.
    1. Raju B.L., Lin S.J., Hou W.C., Lai Z.Y., Liu P.C., Hsu F.L. Antioxidant iridoid glucosides from Wendlandia formosana. Nat. Prod. Res. 2004;18:357–364. doi: 10.1080/14786410310001622013.
    1. Mody N., Parhami F., Sarafian T.A., Demer L.L. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radical. Bio. Med. 2001;31:509–519. doi: 10.1016/S0891-5849(01)00610-4.
    1. Kim H.M., An C.S., Jung K.Y., Choo Y.K., Park J.K., Nam S.Y. Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes. Pharmacol. Res. 1999;40:171–176. doi: 10.1006/phrs.1999.0504.
    1. Evans D.B., Bunning R.A., Russell R.G. The effects of recombinant human interleukin-1 beta on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alkaline phosphatase by osteoblast-like cells derived from human bone. Biochem. biophysical Res. Commun. 1990;166:208–216. doi: 10.1016/0006-291X(90)91932-I.
    1. Stashenko P., Dewhirst F.E., Peros W.J., Kent R.L., Ago J.M. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J. Immunol. 1987;138:1464–1468.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe