Sains Malaysiana 45(12)(2016): 1815–1822

http://dx.doi.org/10.17576/jsm-2016-4512-05

 

Tindakan Minyak Kelapa Dara terhadap Tulang Osteoporosis Pascamenopaus: Analisis

Gen Osteoblastogenesis dan Antioksidan

(The Effects of Virgin Coconut Oil on Postmenopausal Osteoporotic Bone: Analyses on Osteoblastogenesis and Antioxidant Genes)

 

SHIDQIYYAH ABDUL-HAMID^1,2, NORLIZA MUHAMMAD¹* & ISA NAINA MOHAMED¹

 

¹Jabatan Farmakologi, Fakulti Perubatan, Bangunan Pra-Klinikal PPUKM, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, 56000 Kuala Lumpur, Wilayah Persekutuan, Malaysia

 

²Department of Basic Medical Sciences for Nursing, Kulliyyah of Nursing, Universiti Islam Antarabangsa Malaysia, 53100 Kuala Lumpur, Wilayah Persekutuan, Malaysia

 

Diserahkan: 16 September 2015/Diterima: 29 April 2016

 

ABSTRAK

Osteoporosis pascamenopaus merupakan salah satu masalah kesihatan utama yang melanda kaum wanita berumur. Ia disebabkan oleh beberapa faktor termasuk tekanan oksidatif, yang dipercayai dapat dikawal melalui pengambilan antioksidan daripada sumber makanan. Minyak kelapa dara (VCO) merupakan salah satu hasil semula jadi yang kaya dengan antioksidan dan telah dibuktikan mampu memelihara tulang yang mengalami osteoporosis. Kajian ini dijalankan untuk mendapatkan kefahaman yang lebih mendalam tentang aktiviti minyak kelapa dara terhadap osteoporosis pada peringkat molekular. Tiga puluh dua ekor tikus betina Sprague-Dawley dibahagikan kepada empat kumpulan, iaitu kumpulan pembedahan Sham, kawalan terovariektomi (Ovx+Ctrl), kumpulan terovariektomi dengan rawatan VCO (Ovx+VCO) dan kumpulan terovariektomi dengan rawatan estrogen (Ovx+E). Kesemua rawatan diberikan melalui oral selama sepuluh minggu. Sampel tulang femur tikus diambil untuk mengkaji perubahan pada ekspresi gen superoksida dismutase (SOD), glutation peroksidase (GPX), osteokalsin dan transkripsi faktor 2 berkaitan run (Runx2). Hasil kajian mendapati bahawa tikus yang menerima rawatan VCO mengalami peningkatan yang signifikan pada ekspresi gen SOD, GPX dan osteokalsin berbanding kumpulan kawalan terovariektomi, disamping ekspresi gen Runx2 yang turut menunjukkan pola peningkatan. Secara kesimpulannya, VCO membantu memelihara tulang pada tikus model osteoporosis melalui tindakannya meningkatkan ekspresi gen antioksidan serta gen yang menigkatkan aktiviti sel osteoblas.

 

Kata kunci: Minyak kelapa dara; model tikus terovariektomi; osteoporosis; pascamenopaus

 

ABSTRACT

Postmenopausal osteoporosis is one of the main health problems in aging women. It was due to several factors including oxidative stress, which can be controlled through intake of antioxidants from food sources. Virgin coconut oil (VCO) is one of the natural product rich in antioxidants and has been proven to protect osteoporotic bone. This study was conducted to gain in-depth understanding on virgin coconut oil’s activity on osteoporosis at molecular level. Thirty two female Sprague-Dawley rats were divided into four groups, namely Sham operated group, ovariectomized control group (Ovx+Ctrl), ovariectomized with VCO treatment (Ovx+VCO), and ovariectomized with estrogen treatment (Ovx+E). All treatments were administered orally for ten weeks. Bone samples were obtained to examine changes on expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), osteocalcin and runt-related transcription factor 2 (Runx2) genes. The results indicated that rats receiving VCO treatment had experienced significant increments in SOD, GPX and osteocalcin gene expressions compared to the ovariectomized control group, besides the gene expressions of Runx2 which also showed an increment pattern. In conclusion, VCO helps to protect bone in osteoporotic rat model by increasing the expressions of antioxidant genes and genes which increase the osteoblast acitivities.

 

Keywords: Osteoporosis; ovariectomized rat model; postmenopausal; virgin coconut oil

RUJUKAN

Abujazia, M.A., Muhammad, N., Shuid, A.N. & Soelaiman, I.N. 2012. The effects of virgin coconut oil on bone oxidative status in ovariectomised rat. Evidence-Based Complementary and Alternative Medicine: eCAM 2012 (January): 525079.

Aggarwal, N., Raveendran, A., Khandelwal, N., Sen, R.K., Thakur, J.S., Dhaliwal, L.K., Singla, V. & Manoharan, S.R. 2011. Prevalence and related risk factors of osteoporosis in peri- and postmenopausal Indian women. Journal of Mid-Life Health 2(2): 81-85.

Almeida, M. 2010. Aging and oxidative stress: A new look at Old Bone. IBMS BoneKEy 7(10): 340-352.

Arai, M., Shibata, Y., Pugdee, K., Abiko, Y. & Ogata, Y. 2007. Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 Cells. IUBMB Life 59(1): 27-33.

Arunima, S. & Rajamohan, T. 2012. Virgin coconut oil improves hepatic lipid metabolism in rats--compared with copra oil, olive oil and sunflower oil. Indian Journal of Experimental Biology 50(11): 802-809.

Baek, K-H., Oh, K-W., Lee, W-Y., Lee, S-S., Kim, M-K., Kwon, H-S., Rhee, E-J., Han, J-H., Song, K-H., Cha, B.Y., Lee, K.W. & Kang, M.I. 2010. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcified Tissue International 87(3): 226-235.

Behfar, A.A., Sadeghi, N., Oveisi, M.R., Janat, B., Hajimahmoodi, M., Jamshidi, A.R., Behzad, M. & Rastegary, P. 2008. The plasma antioxidant activity of superoxide dismutase enzyme in osteoporosis. Acta Medica Iranica 46(6): 441-446.

Bellanti, F., Matteo, M., Rollo, T., De Rosario, F., Greco, P., Vendemiale, G. & Serviddio, G. 2013. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy. Redox Biology 1(1): 340-346.

Bu, S.Y., Hunt, T.S. & Smith, B.J. 2009. Dried plum polyphenols attenuate the detrimental effects of TNF-alpha on osteoblast function coincident with up-regulation of Runx2, osterix and IGF-I. The Journal of Nutritional Biochemistry 20(1): 35-44.

Cao, Y., Zhou, Z., de Crombrugghe, B., Nakashima, K., Guan, H., Duan, X., Jia, S-F. & Kleinerman, E.S. 2005. Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in Murine osteosarcoma. Cancer Research 65(4): 1124-1128.

Chen, J.R., Lazarenko, O.P., Wu, X., Kang, J., Blackburn, M.L., Shankar, K., Badger, T.M. & Ronis, M.J. 2010. Dietary-induced serum phenolic acids promote bone growth via p38 MAPK/b-catenin canonical Wnt signaling. Journal of Bone and Mineral Research 25(11): 2399-2411.

Datta, H.K., Ng, W.F., Walker, J.A., Tuck, S.P. & Varanasi, S.S. 2008. The cell biology of bone metabolism. Journal of Clinical Pathology 61(5): 577-587.

Dia, V.P., Garcia, V.V. & Mabesa, R.C. 2005. Comparative physiological characteristics of virgin coconut oil produced by different methods. Philippine Agricultural Scientist 88(1): 462-475.

Duthie, G.G., Duthie, S.J. & Kyle, J.A. 2000. Plant polyphenols in cancer and heart disease: Implications as nutritional antioxidants. Nutrition Research Reviews 13(1): 79-106.

Eastell, R. 2013. Identification and management of osteoporosis in older adults. Medicine 41(1): 47-52.

Franklin, M., Bu, S.Y., Lerner, M.R., Lancaster, E.A., Bellmer, D., Marlow, D., Lightfoot, S.A., Arjmandi, B.H., Brackett, D.J., Lucas, E.A. & Smith, B.J. 2006. Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway. Bone 39(6): 1331-1342.

Gaur, T., Lengner, C.J., Hovhannisyan, H., Bhat, R.A., Bodine, P.V., Komm, B.S., Javed, A., van Wijnen, A.J., Stein, J.L., Stein, G.S. & Lian, J.B. 2005. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. The Journal of Biological Chemistry 280(39): 33132-33140.

Hayatullina, Z., Muhammad, N., Mohamed, N. & Soelaiman, I.N. 2012. Virgin coconut oil supplementation prevents bone loss in osteoporosis rat model. Evidence-Based Complementary and Alternative Medicine: eCAM 2012 (January): 237236.

Høegh-Andersen, P., Tankó, L.B., Andersen, T.L., Lundberg, C.V., Mo, J.A., Heegaard, A-M., Delaissé, J-M. & Christgau, S. 2004. Ovariectomized rats as a model of postmenopausal oasteoarthritis: Validation and application. Arthritis Research & Therapy 6(2): R169-180.

Jagger, C.J., Lean, J.M., Davies, J.T. & Chambers, T.J. 2005. Tumor necrosis factor-alpha mediates osteopenia caused by depletion of antioxidants. Endocrinology 146(1): 113-118.

Jee, W.S.S. 1995. Animal models in the prevention and treatment of osteopenia: Forward. Proceedings of the International Conference on Animal Models in the Prevention and Treatment of Osteopenia. Cairns, Australia, February 11-13. Bone 17(4): S113-114.

Kamariah, L., Azmi, A., Rosmawati, A., Wai Ching, M.G., Azlina, M.D., Sivapragasam, A., Tan, C.P. & Lai, O.M. 2008. Physico-chemical and quality characteristics of virgin coconut oil - A Malaysian survey. J. Trop. Agric. and Fd. Sc. 36(2): 239-248.

Kaveh, Kamran, Rashid Ibrahim, Mohd Zuki Abubakar & Tengku Azmi Ibrahim. 2010. Osteoporosis induction in animal model. American Journal of Animal and Veterinary Sciences 5(2): 139-145.

Lean, J.M., Davies, J.T., Fuller, K., Jagger, C.J., Kirstein, B., Partington, G.A., Urry, Z.L. & Chambers, T.J. 2003. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. The Journal of Clinical Investigation 112(6): 915-923.

Lelovas, P.P., Xanthos, T.T., Thoma, S.E., Lyritis, G.P. & Dontas, I.A. 2008. The laboratory rat as an animal model for osteoporosis research. Comparative Medicine 58(5): 424-430.

Liau, K.M., Lee, Y.Y., Chen, C.K. & Rasool, A.H. 2011. An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity. ISRN Pharmacology 2011(January): 1-7.

Lim, P.S., Ong, F.B., Adeeb, N., Seri, S.S., Noor-Aini, M.Y., Shamsuddin, K., Hapizah, N., Mohamed, A.L., Mokhtar, A. & Wan, H.W.H. 2005. Bone health in urban midlife Malaysian women: Risk factors and prevention. Osteoporosis International 16(12): 2069-2079.

Maggio, D., Barabani, M., Pierandrei, M., Polidori, M.C., Catani, M., Mecocci, P., Senin, U., Pacifici, R. & Cherubini, A. 2003. Marked decrease in plasma antioxidants in aged osteoporotic women: Results of a cross-sectional study. Journal of Clinical Endocrinology & Metabolism 88(4): 1523-1527.

Manolagas, S.C. 2010. From estrogen-centric to aging and oxidative stress : A revised perspective of the pathogenesis of osteoporosis. Endocrine Reviews 31(2010): 266-300.

Mansor, T.S.T., Che Man, Y.B., Shuhaimi, M., Abdul Afiq, M.J. & Ku Nurul, F.K.M. 2012. Physicochemical properties of virgin coconut oil extracted from different processing methods. International Food Research Journal 19(3): 837-845.

Marina, A.M., Che Man, Y.B., Nazimah, S.A.H. & Amin, I. 2009. Antioxidant capacity and phenolic acids of virgin coconut oil. International Journal of Food Sciences and Nutrition 60(S2): 114-123.

Miller, S.C., Bowman, B.M. & Jee, W.S.S. 1995. Available animal models of osteopenia - Small and large. Bone 17(4): S117-123.

Muthusami, S., Ramachandran, I., Muthusamy, B., Vasudevan, G., Prabhu, V., Subramaniam, V., Jagadeesan, A. & Narasimhan, S. 2005. Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats. Clinica Chimica Acta 360(1-2): 81-86.

Naylor, K. & Eastell, R. 2012. Bone turnover markers: Use in osteoporosis. Nature Reviews Rheumatology 8(7): 379-389.

Nevin, K.G. & Rajamohan, T. 2010. Effect of topical application of virgin coconut oil on skin components and antioxidant status during dermal wound healing in young rats. Skin Pharmacology and Physiology 23(6): 290-297.

Nevin, K.G. & Rajamohan, T. 2008. Influence of virgin coconut oil on blood coagulation factors, lipid levels and LDL oxidation in cholesterol fed Sprague-Dawley rats. E-SPEN, the European E-Journal of Clinical Nutrition and Metabolism 3(1): e1-e8.

Nevin, K.G. & Rajamohan, T. 2006. Virgin coconut oil supplemented diet increases the antioxidant status in rats. Food Chemistry 99(2): 260-266.

Novack, D.V. & Faccio, R. 2011. Osteoclast motility: Putting the brakes on bone resorption. Ageing Research Reviews 10(1): 54-61.

Oveisi, M.R., Sadeghi, N., Jannat, B., Hajimahmoodi, M., Hdjibabaie, M. & Behfar, A. 2011. Evaluation of antioxidants in bone mineral density of Iranian osteoporotic women. Iranian Journal of Basic Medical Sciences 14(2): 158-166.

Puel, C., Quintin, A., Agalias, A., Mathey, J., Obled, C., Mazur, A., Davicco, M.J., Lebecque, P., Skaltsounis, A.L. & Coxam, V. 2004. Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat. The British Journal of Nutrition 92(1): 119-127.

Raisz, L.G. 2005. Science in medicine pathogenesis of osteoporosis : Concepts, conflicts, and prospects. The Journal of Clinical Investigation 115(12): 3318-3325.

Rao, L.G., Kang, N. & Rao, A.V. 2012. Review. In SpringerReference, edited by Dr Venketeshwer Rao, InTech. Springer. pp. 467-486.

Reagan-Shaw, S., Nihal, M. & Nihal, A. 2007. Dose translation from animal to human studies revisited. FASEB Journal 22(3): 659-661.

Rendina, E., Hembree, K.D., Davis, M.R., Marlow, D., Clarke, S.L., Halloran, B.P., Lucas, E.A. & Smith, B.J. 2013. Dried plum’s unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model. PloS One 8(3): e60569.

Riggs, B.L., Khosla, S. & Melton, L.J. 2002. Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviews 23(3): 279-302.

Sánchez-Rodríguez, M.A., Ruiz-Ramos, M., Correa-Muñoz, E. & Mendoza-Núñez, V.M. 2007. Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskeletal Disorders 8: 124.

Sen, S., Raja Chakraborty, Sridhar, C., Reddy, Y.S.R. & Biplab De. 2010. Free radicals, antioxidants, diseases and phytomedicines: Current status and future prospect nitrogen species. International Journal of Pharmaceutical Sciences Review and Research 3(1): 91-100.

Shen, C-L., Yeh, J.K., Cao, J.J., Chyu, M-C. & Wang, J-S. 2011. Green tea and bone health: Evidence from laboratory studies. Pharmacological Research 64(2): 155-161.

Shen, C-L., Wang, P., Guerrieri, J., Yeh, J.K. & Wang, J-S. 2008. Protective effect of green tea polyphenols on bone loss in middle-aged female rats. Osteoporosis International 19(7): 979-990.

Weatherholt, A.M., Fuchs, R.K. & Warden, S.J. 2012. Specialized connective tissue: Bone, the structural framework of the upper extremity. Journal of Hand Therapy 25(2): 123-131.

Wu, W-T., Lee, R-P., Wang, C-H., Fang, T-C., Lin, N-T., Chen, I-H. & Hsu, B-G. 2010. The association of serum osteoprotegerin and osteoporosis in postmenopausal hemodialysis patients: A pilot study. Journal of Women’s Health 19(4): 785-790.

Xiao, G., Wang, D., Benson, M.D., Karsenty, G. & Franceschi, R.T. 1998. Role of the α2-Integrin in osteoblast-specific gene expression and activation of the Osf2 transcription factor. Journal of Biological Chemistry 273(49): 32988-32994.

Yarrow, J.F., Conover, C.F., Purandare, A.V., Bhakta, A.M., Zheng, N., Conrad, B., Altman, M.K., Franz, S.E., Wronski, T.J. & Borst, S.E. 2008. Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats. American Journal of Physiology. Endocrinology and Metabolism 295(5): E1213-E1222.

Yoon, K-H., Cho, D-C., Yu, S-H., Kim, K-T., Jeon, Y. & Sung, J-K. 2012. The change of bone metabolism in ovariectomized rats: Analyses of microCT scan and biochemical markers of bone turnover. Journal of Korean Neurosurgical Society 51(6): 323-327.

Zhang, C., Tang, W., Li, Y., Yang, F., Dowd, D.R. & MacDonald, P.N. 2011. Osteoblast-specific transcription factor osterix increases vitamin D receptor gene expression in osteoblasts. PloS One 6(10): e26504.

 

 

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