Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2015 | Research article

Time and dose-dependent effects of Labisia pumila on the bone strength of postmenopausal osteoporosis rat model

Authors: Nadia Mohd Effendy, Shahrum Abdullah, Mohd Faridz Mod Yunoh, Ahmad Nazrun Shuid

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

Abstract

Background

Post-menopausal osteoporosis has long been treated and prevented by estrogen replacement therapy (ERT). Despite its effectiveness, ERT is associated with serious adverse effects. Labisia pumila var. alata (LP) is a herb with potential as an alternative agent to ERT due to its phytoestrogenic, antioxidative and anti-inflammatory effects on bone. This study aimed to determine the effects of LP supplementation on bone biomechanical strength of postmenopausal osteoporosis rat model.

Methods

Ninety-six female Sprague–Dawley rats aged 4 to 5 months old were randomly divided into six groups; six rats in the baseline group (BL) and eighteen rats in each group of; Sham- operated (Sham), ovariectomised control (OVXC) and ovariectomised with daily oral gavages of Premarin at 64.5 μg/kg (ERT), LP at 20 mg/kg (LP20) and LP at 100 mg/kg (LP100) respectively. These groups were subdivided into three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out for biomechanical strength analysis using Instron Universal Model 5848 Micro Tester.

Results

OVXC group showed deterioration in the bone biomechanical strength with time. Both ERT and LP supplemented rats showed improvements in bone strength parameters such as maximum load, displacement, stiffness, stress, and Young Modulus. The most improved bone strength was seen in rats given LP at the dose of 100 mg/kg for nine weeks.

Conclusion

LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone biomechanical changes.

Christiansen C. Consensus Development Conference: prophylaxis and treatment of osteoporosis. Am J Med. 1991;90(1):107–10.

Koh LK, Saw SM, Lee JJ, Leong KH, Lee J. Hip fractures incidence rates in Singapore 1991–1998. Osteoporos Int. 2001;12(4):311–8.PubMed

Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–7.PubMed

Melton 3rd LJ. Who has osteoporosis? A conflict between clinical and public health perspectives. J Bone Miner Res. 2000;15:2309.PubMed

Henrik GA, Bjӧrn ER, Teppo LNJ, Cecilia R, Jan-Ake N, Ingemar S, et al. Prevalence of osteoporosis and incidence of hip fracture in women-secular trends over 30 years. BMC Musculoskelet Disord. 2010;11(48):1–7.

Osteoporosis Australia. 2004. http://www.osteoporosis.org.au

Rohr UD. The impact of testosterone imbalance on depression and women’s health. Maturitas. 2002;41 Suppl 1:S25–46.PubMed

Parves T. Postmenopausal osteoporosis. JK-Practitioner. 2004;11(4):281–3.

Jilka RL. Cytokines, bone remodelling and estrogen deficiency. Bone. 1998;23(2):75–81.PubMed

10.

Pfeilschifter J, Koditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocrinol Rev. 2002;23:90–119.

11.

Bart C. Normal bone anatomy & physiology. Clin J Am Soc Nephrol. 2008;3:S131–9.

12.

Iain HK. Principles of bone healing. Neurosurg Focus. 2001;10(4):1–8.

13.

Khastgir G, Studd J, Holland N. Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: Histomorphometric evidence in a longitudinal study. J Clin Endocrinol Metabol. 2001;86:289–95.

14.

Shumaker SA, Legault C, Rapp R, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory: a randomized controlled trial. JAMA. 2003;289(20):2651–62.PubMed

15.

Al-Azzawi F. Prevention of postmenopausal osteoporosis and associated fractures: Clinical evaluation of the choice between estrogen and bisphosphonates. Gynecol Endocrinol. 2008;24(11):601–9.PubMed

16.

Komm BS, Chines AA. An update on selective estrogen receptor modulators for the prevention and treatment of osteoporosis. Maturitas. 2010;71(3):221–6.

17.

Cano A, Dapia S, Noguela J, Pineda B, Hermenegildo C, del Val R, et al. Comparative effects of 17β-estradiol, raloxifene and genistein on bone 3D mircroarchitecture and volumetric bone mineral density in ovariectomized mice. Osteoporos Int. 2008;19:793–800.PubMed

18.

Roussow JE, Anderson GL, Prentice RL, LaCroix A, Kooperberg C, Stefanick ML. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–33.

19.

Wassertheil-Smoller S, Hendrix SL, Limacher M. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA. 2003;289:2673–84.PubMed

20.

Chlebowski RT, Hendrix SL, Langer RD. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA. 2003;289:3243–53.PubMed

21.

Henry GB. Selective oestrogen receptor modulators. Horm Res. 2000;53:25–9.

22.

FDA Approves New Uses for Evista (Press release). U.S. Food and Drug Administration. 2007-09-14.

23.

Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, et al. Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone. 2003;33:522–32.PubMed

24.

Kanis JA, Johnell O, Black DM, Downs Jr RW, Sarkar S, Fuerst T, et al. Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial. Bone. 2003;33:293–300.PubMed

25.

Johnell O, Scheele WH, Lu Y, Reginster J-Y, Need AG, Seeman E. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87:985–92.PubMed

26.

Turner RT, Rickard DJ, Iwaniec UT, Spelsberg TC. Estrogens and progestins. In: Bilezikian JP, Raisz LG, Martin TJ, editors. Principles of bone biology. 3rd ed. USA: Academic Pres; 2008.

27.

Yan MZ, Xu Y, Gong YX, Liu JM, Lu SY, Huang L, et al. Raloxifene inhibits bone loss and improves bone strength through an OPg-independent mechanism. Endocrine. 2010;37(1):55–61.PubMed

28.

Delmas PD, Ensrud KE, Adachi JD. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: Four-year results from a randomized clinical trial. J Clin Endocrinol Metabol. 2002;87:3609–17.

29.

Grady D, Ettinger B, Moscarelli E. Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol. 2004;104:837–44.PubMed

30.

Vogel V, Joseph C, Lawrence W. Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes. J Am Med Assoc. 2006;295(23):2727–41.

31.

Reginster J, Minne HW, Sorensen OH. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11:83–91.PubMed

32.

Stevenson M, Jones ML, De Nigris E, Brewer N, Davis S, Oakley J. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess. 2005;9:1–160.PubMed

33.

Reiner B, Bertha F, Emmo VT, Christoph B. Biphosphonates in Medical Practice. New York: Springer; 2007.

34.

Khosla S, Burr D, Cauley J. Bisphosphonate-associated osteonecrosis of the jaw: report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479–91.PubMed

35.

Zakaria M, Mohd MA. Traditional Malay Medicinal Plants. Kuala Lumpur, Malaysia: Penerbit Fajar Bakti; 1994.

36.

Bodeker G. Health and Beauty from the Rainforest: Malaysian Traditions of Ramuan. Kuala Lumpur, Malaysia: Editions Didier Millet Pty; 1999.

37.

Fasihuddin A, Rahman AH, Hasmah R. Medicinal plants used by bajau community in sabah. In: Chan KL, editor. Trends in Traditional Medicine Research. Penang, Malaysia: The School of Pharmaceutical Sciences, University of Science Malaysia; 1995. p. 493–504.

38.

Jamal JA, Houghton PJ, Milligan SR. Testing of labisia pumila for oestrogenic activity using a recombinant yeast screen. J Pharm Pharmacol. 1998;50:79.

39.

Karimi E, Jaafar HZ, Ahmad S. Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of labisia pumila benth: from microwave obtained extracts. BMC Complement Altern Med. 2013;13(20):1–10.

40.

Burkill IH. Dictionary of the Economic Products of the Malay Peninsula. London: Publisher Crown Agents for the Colonies; 1935.

41.

Rasadah MA, Zainon AS. Database on ASEAN Herbal and Medicinal Plants, ASEAN Publication. 2003.

42.

Whitten PL, Kudo S, Okubo KK. Isoflavonoids. In: D’ Mello JPF, editor. Handbook of Plant and FUngal Toxicants. Boca Raton: CRC Press; 1997.

43.

Pfitscher A, Reiter E, Jungbauer A. Receptor binding and transactivation activities of red clover isoflavones and their metabolites. J Steroid Biochem Mol Biol. 2008;112:87–94.PubMed

44.

Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008;74:1656–65.PubMedPubMedCentral

45.

Degen GH, Janning P, Diel P, Bolt HM. Estrogenic isoflavones in rodent diets. Toxicol Lett. 2002;128:145–57.PubMed

46.

Karkola S, Lilienkampf A, Wähälä K. Phytoestrogens in drug discovery for controlling steroid biosynthesis. In: Daayf F, Lattanzio V, editors. Recent Advances in Polyphenol Research. Oxford, UK: Wiley-Blackwell; 2009.

47.

Nazrun AS, Lee PL, Norliza M, Norazlina M, Ima Nirwana S. The effects of Labisia pumila var. alata on bone markers and bone calcium in a rat model of post-menopausal osteoporosis. J Ethnopharmacol. 2011;133(2):538–42.

48.

Fathilah SN, Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S. Labisia pumila protects the bone of estrogen-deficient rat model: A histomorphometric study. J Ethnopharmacol. 2012;142:294–9.PubMed

49.

Binkley N, Bilezikian JP, Kendler DL, Leib ES, Lewiecki EM, Petak SM. International Society for Clinical Densitometry. Official positions of the International Society for Clinical Densitometry and executive summary of the 2005 Position Development Conference. J Clin Densitom. 2006;9:4–14.PubMed

50.

Kanis JA, Glüer CC, for the Committee of Scientific Advisors. International Osteoporosis Foundation. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int. 2000;11:192–202.PubMed

51.

National Osteoporosis Foundation (NOF). Physician’s Guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2003.

52.

Voide R, Van Lenthe H, Schneider P, Thurner P, Wyss P, Sennhauser U, et al. Functional Microimaging: an integrated approach for advanced bone biomechanics and failure analysis. In: Armando M, Amir AA, editors. Medical Imaging: Physiology, Function and Structure from Medical Images. San Diego: Proc SPIE 6143; 2006.

53.

Grant B, Tony MK. Trabecular bone strength predictions using finite element analysis of micro-scale images at limited spatial resolution. Bone. 2009;44:579–84.

54.

Joshua AM, Steven KB. Bone strength at the distal radius can be estimated from high resolution peripheral quantitative computed tomography and the finite element method. Bone. 2008;42:1203–13.

55.

Helene B, Eric L, Claude-Laurent B. Evaluation of macrostructural bone biomechanics. Joint Bone Spine. 2007;74:233–9.

56.

Vijender A, Dharmendra G. Recent update on osteoporosis. Int J Med Sci Public Health. 2013;2(2):164–8.

57.

Melton LJ, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL. Prevalence and incidence of vertebral deformities. Osteoporos Int. 1993;3:113–9.PubMed

58.

Nadia ME, Fadhli MK, Ima Nirwana S, Nazrun AS. The effects of Labisia pumila on postmenopausal osteoporotic rat model: Dose and time-dependent micro-CT analysis. J X-ray Sci Technol. 2014;22(4):503–18.

59.

Bohatyrewicz A. Effects of fluoride on mechanical properties of femoral bone in growing rats. Fluoride. 1999;32:47–54.

60.

Chacha D, Turner CH, Dunipace AJ, Grynpas MD. The effect of fluoride treatment on bone mineral in rabbits. Calcif Tissue Int. 1999;64:345–51.

61.

Ammann P, Rizzoli R. Bone strength and its determinants. Osteoporos Int. 2003;14(3):13–8.

62.

Sambrook PN, Cameron ID, Chen JS, Cumming RG, Lord SR, March LM, et al. Influence of fall related fractures and bone strength on fracture risk in the frail elderly. Osteoporos Int. 2007;18:603–10.PubMed

63.

Jacqueline HC, Marjolein CH van der M. Whole bone mechanics and bone quality. Clin Orthop Relat Res. 2011;469:2139–49.

64.

Riggs BL. The mechanisms of estrogen regulation of bone resorption. J Clin Investig. 2000;106(10):1203–4.PubMedPubMedCentral

65.

Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Investig. 2000;106(12):1553–60.PubMedPubMedCentral

66.

Zi-xiang W, Wei L, Yun-yu H, Hai-qiang W, Shi-yong W, Zhen-sheng M, et al. Effect of ovariectomy on BMD, micro-architecture and biomechanics of cortical and cancellous bones in a sheep model. Med Eng Phys. 2008;30:1112–8.

67.

Parfitt AM. Age-related structural changes in trabecular and corticalbone: cellular mechanisms and biomechanical consequences. Calcif Tissue Int. 1984;36 Suppl 1:123–8.

68.

Augat P, Link T, Lang TF, Lin JC, Majumdar S, Genant HK. Anisotropy of the elastic modulus of trabecular bone specimens from different anatomical locations. Med Eng Phys. 1998;20:124–31.PubMed

69.

Kennedy OD, Brennan O, Rackard SM, Staines A, O’Brien FJ, Taylor D, et al. Effects of ovariectomy on bone turnover, porosity and biomechanical properties in ovine compact bone 12 months postsurgery. J Orthop Res. 2009;27(3):303–9.PubMed

70.

Grumbach MM. Estrogen, bone, growth and sex: a sea change in conventional wisdom. J Pediatr Endocrinol Metab. 2000;13 Suppl 6:1439–55.PubMed

71.

Gautam K, Joh S, Nigel H, Jamshid A-Z, Simon F, Jade C. Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: Histomorphometric evidence in a longitudinal study. J Clin Endocrinol Metabol. 2001;86(1):289–95.

72.

Okazaki R, Inoue D, Shibata M, Saika M, Kido S, Ooka H, et al. Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta. Endocrinology. 2002;143(6):2349–56.PubMed

73.

Bord S, Irelan DC, Beaven SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL and estrogen receptor expression in human osteoblasts. Bone. 2003;32(2):136–41.PubMed

74.

Mitani M, Miura Y, Saura R, Kitagawa A, Fukuyama T, Hashiramoto A, et al. Estrogen specifically stimulates expression and production of osteoprotegrin from rheumatoid synovial fibroblasts. Int J Mol Med. 2005;15(5):827–32.PubMed

75.

Badeau M, Adlercreutz H, Kaihovaara P, Tikkanen MJ. Estrogen A-ring structure and antioxidative effect on lipoproteins. J Steroid Biochem Mol Biol. 2005;96(3–4):271–8.PubMed

76.

Wan Ezumi MF, Siti Amrah S, Suhaimi AW, Mohsin SSJ. Evaluation of the female reproductive toxicity of aqueous extract of Labisia pumila var. alata in rats. Indian J Pharm. 2007;39(1):30–2.

77.

Singh GD, Ganjoo M, Youssouf MS, Koul A, Sharma R, Singh S, et al. Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb. Food Chem Toxicol. 2009;47(10):2661–5.PubMed

78.

Taneja SC. Sub-Chronic (90 days) Oral Toxicity Studies of Aqueous Extract of Labisia pumila in Wistar Rats (250, 500&1000 mg/kg b. wt. only). India: Indian Institute of Integrative Medicine Jammu; 2004.

79.

Richard MA. Mechanical testing of bone ex vivo. In: Helfrich MH, Ralston SH, editors. Methods in Molecular Medicine. Bone Research Protocols. Totowa, New Jersey: Humana Press; 2003. p. 369–77.

80.

Waarsing JH, Day JS, Linden van der, Ederveen AG, Spanjers C, Clerck ND, et al. Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. Bone. 2004;34(1):163–9.PubMed

81.

Hernandez CH, Keavenly TM. A biomechanical perspective on bone quality. Bone. 2006;39(6):1173–81.PubMedPubMedCentral

82.

Charles HT. Bone strength: current concepts. Ann N Y Acad Sci. 2006;1068:429–46.

83.

Wendlova J. Bone quality, elasticity and strength. Bratisl Lek Listy. 2008;109(9):383–6.PubMed

84.

Robert OR, Markus JB, Paul H. Plasticity and toughness in bone. Phys Today. 2009;62(6):4.

85.

Gleeson JP, Plunkett NA, O’Brien FJ. Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration. Eur Cell Mater. 2010;20:218–30.PubMed

86.

Mosekilde L, Danielsen CC, Knudsen UB. The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats. Bone. 1993;14(1):1–6.PubMed

87.

88.

Keavenly TM, Wachtel EF, Kopperdahl DL. Mechanical behaviour of damaged trabecular bone. J Biomech. 1999;27(11):1309–18.

89.

Tony MK, Elise FM, Oscar CY. Bone Mechanics in Standard Handbook of Biomedical Engineering and Design. New York: McGraw Hill; 2004.

90.

Hertrampf T, Schleipen B, Offermanns C, Velders M, Laudenbach U, Diel P. Comparison of the bone protective effects of an isoflavone-rich diet with dietary and subcutaneous administrations of genistein in ovariectomized rats. Toxicol Lett. 2009;184(3):198–203.PubMed

91.

Avula B, Wang YH, Ali Z, Smillie TJ, Khan IA. Quantitative determination of triperpene saponins and alkenated-phenolics from Labisia pumila by LCUV/ELSD method and confirmation by LC-ESI-TOF. Planta Med. 2010;76:25.

92.

Ososki AL, Kenelly EJ. Phytoestrogens: a review of the present state of research. Phytother Res. 2003;17:845–69.PubMed

93.

Cos P, De Bruyne T, Apers S, Vanden BD, Pieters L, Vlietinck AJ. Phytoestrogens recent developments. Planta Med. 2003;69:589–99.PubMed

94.

Cassidy A, Albertazzi P, Lise Nielsen I, Hall W, Williamson G, Tetens I, et al. Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. Proc Nutr Soc. 2006;65(1):76–92.PubMed

95.

Bahram HA. The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. J Am Coll Nutr. 2001;20 Suppl 5:3985–4025.

96.

Norhaiza M, Maziah M, Hakiman M. Antioxidative properties of leaf extracts of a popular Malaysian herb, Labisia pumila. J Med Plant Res. 2009;3(4):217–23.

97.

Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. New York: Oxford University Press; 2007.

98.

Jamal J, Houghton P, Milligan S, Ibrahim J. The estrogenic and cytotoxic effects of the extracts of Labisia pimula var. alata and Labisia pumila var. pumila in-vitro. Malays J Health Sci. 2003;1:53–60.

99.

Melissa PSW, Navaratnam V, Yin CY. Estrogenic assessment of Labisia pumila extracts using a human endometrial cell line. Int J Pharm Pharmaceut Sci. 2013;5(2):448–52.

Title: Time and dose-dependent effects of Labisia pumila on the bone strength of postmenopausal osteoporosis rat model
Authors: Nadia Mohd Effendy
Shahrum Abdullah
Mohd Faridz Mod Yunoh
Ahmad Nazrun Shuid
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-015-0567-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Time and dose-dependent effects of Labisia pumila on the bone strength of postmenopausal osteoporosis rat model

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2015

A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury

Exploring new pharmacology and toxicological screening and safety evaluation of one widely used formulation of Nidrakar Bati from South Asia region

Effects of organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis

Training in ChiRunning to reduce blood pressure: a randomized controlled pilot study

In vitro antiviral activity against rotavirus and astrovirus infection exerted by substances obtained from Achyrocline bogotensis (Kunth) DC. (Compositae)

Pattern of traditional medicine use by adult Saudi patients with neurological disorders