THE OSTEOPROTECTIVE EFFECT OF Azadirachta excelsa LEAVES EXTRACT ON BONE OF STREPTOZOTOCIN-INDUCED DIABETIC RATS

Nur Syimal`ain Azmi, Nooraain Hashim, Nurdiana Samsulrizal, Noor Syaffinaz Noor Mohamad Zin

Abstract


Insulin signalling in bone favours whole-body glucose homeostasis by activating osteocalcin, which is important for bone remodeling. However, diabetes causes deficient production of insulin which consequently affects the osteocalcin and bone turnover marker. The aim of this study was to explore the potential of A. excelsa to improve insulin and osteocalcin secretion, resulting in improved bone histomorphometric and bone turnover marker in STZ- induced diabetic rats. The experimental rats were divided into normal control (NC), diabetic control (DC), Metformin-treated diabetic (DMET) (positive control) and A. excelsa-treated diabetic (DAE) rats with the treatment period of eight weeks. After the treatment, the femoral bones were removed and bone morphometrical parameters  were defined using Micro-CT scan. The bones were analysed for mineral density (BMD) and trabecular parameters. The bones samples were decalcified for histological preparation and  images of the  was hematoxylin and eosin (H&E) stained bones were captured and analysed. The concentrations of serum insulin, osteocalcin and bone turnover marker were evaluated using specific ELISA kits. The study showed that A. excelsa caused a significant increase in insulin and osteocalcin levels. A. excelsa also represents ameliorative effects on trabecular bone of the diabetic rat. The data also demonstrated that with A. excelsa treatment, it moderately restored the balance between bone formation and bone resorption markers. These data confirmed that A. excelsa extract could attenuate the STZ-induced bone loss and reverses the deterioration of bone microarchitecture in diabetic rats. This finding indicates the osteoprotective effects presence in the A. excelsa extract.


Keywords


Azadirachta excelsa, streptozotocin-induced diabetes, bone morphometric, Micro-CT, insulin, osteocalcin

Full Text:

PDF

References


Diabetes Malaysia Association. 2011. Profile of the diadnosed. In What is diabetes. Retrieved March 10, 2019 from http;//www.diabetes.org.my/articles.phd?aid=5.

Hamann, C., Kirschner, S., Günther, K. P., and Hofbauer, L. C. 2012. Bone, Sweet Bone—Osteoporotic Fractures in Diabetes Mellitus. Nature Reviews Endocrinology. 8(5): 297-305.

Lampropoulos, C. E., Papaioannou, I., and D'Cruz, D. P. 2012. Osteoporosis—A Risk Factor for Cardiovascular Disease? Nature Reviews Rheumatology. 8(10): 587-598.

dePaula, F. J., Horowitz, M. C., and Rosen, C. J. 2010. Novel Insights into the Relationship Between Diabetes And Osteoporosis. Diabetes/Metabolism Research and Reviews. 26(8): 622-630.

Karsenty, G., and Ferron, M. 2012. The Contribution of Bone to Whole-organism Physiology. Nature. 481(7381): 314.

Zhen, D., Chen, Y., and Tang, X. 2010. Metformin Reverses the Deleterious Effects of High Glucose on Osteoblast Function. Journal of Diabetes and its Complications. 24(5): 334-344.

Al-Hariri, M. 2016. Sweet Bones: The Pathogenesis of Bone Alteration in Diabetes. Journal of Diabetes Research.

Ghodsi, M., Keshtkar, A. A., Nasli-Esfahani, E., Alatab, S., andMohajeri-Tehrani, M. R. 2016. Mechanisms Involved in Altered Bone Metabolism in Diabetes: A Narrative Review. Journal of Diabetes & Metabolic Disorders. 15(1): 52.

Baucom, K., Pizzorno, L., andPizzorno, J. 2014. Osteoporosis: The Need for Prevention and Treatment. Journal of Restorative Medicine. 3(1): 2-29.

Lecka-Czernik, B. 2010. Bone Loss in Diabetes: Use of Antidiabeticthiazolidinediones and Secondary Osteoporosis. Current Osteoporosis Reports. 8(4): 178-184.

Rizzoli, R., Reginster, J. Y., Boonen, S., Bréart, G., Diez-Perez, A., Felsenberg, D., and Cooper, C. 2011. Adverse Reactions and Drug–drug Interactions in the Management of Women with Postmenopausal Osteoporosis. Calcified Tissue International. 89(2): 91-104.

Horcajada, M. N., Habauzit, V., Trzeciakiewicz, A., Morand, C., Gil-Izquierdo, A., Mardon, J., and Offord, E. 2008. Hesperidin Inhibits Ovariectomized-induced Osteopenia and Shows Differential Effects on Bone Mass and Strength in Young and Adult Intact Rats. Journal of Applied Physiology. 104(3): 648-654.

Peng, X. M., WU, J. C., Zheng, Y. X., and Zhang, Y. P. 2012. A Review on Classification and Distribution of Azadirachta. Journal of Plant Genetic Resources. 13(4): 583-588.

Nurdiana, S., Mohamad Shukri, K., Elizabeth Jega, J. and Nurul`Izzati, S. 2013. Lowering Blood Glucose Effect of Azadirachtaexcelsa Leaves Extract. Natural Products: An Indian Journal. 9(9): 363-366.

Nor Aini A. S. and Seong, L. K. 2006. Azadirachtin Variation of Six Provenances of Azadirachtaexcelsa (Jack) Jacob. Pakistan Journal of Biological Sciences. 9: 833-836.

Nurul ‘Izzati, S., Nurdiana, S., Hafandi, A., MohdZakihalani, A. H., Norashirene M. J. and SitiKhairiyah M. H. 2013. Antioxidant and Hypoglycemic Activities of Azadirachtaexcelsa in Diabetic Rats. ISBEIA 2013: IEEE Symposium on Business, Engineering and Industrial Applications, Kuching. 63.

Zin, N. S. N. M., Hashim, N., Samsulrizal, N., andAzmi, N. S. A. 2018. The Protective Effect of Azadirachtaexcelsa Leaves Extract and Quercetin Treatment on the Learning and Memory Impairments in Relation with Insulin and Amylin Levels in the Brain of Streptozotocin-induced Diabetic Rats. Journal of King Saud University-Science.

Al-Mustafa, A. H., and Al-Thunibat, O. Y. 2008. Antioxidant Activity of some Jordanian Medicinal Plants Used Traditionally for Treatment Of Diabetes. Pak J BiolSci. 11(3): 351-358.

Verdelis, K., Lukashova, L., Atti, E., Mayer-Kuckuk, P., Peterson, M. G. E., Tetradis, S., and van der Meulen, M. C. H. 2011. MicroCT Morphometry Analysis of Mouse Cancellous Bone: Intra-and Inter-system Reproducibility. Bone. 49(3): 580-587.

Bouxsein, M. L., Boyd, S. K., Christiansen, B. A., Guldberg, R. E., Jepsen, K. J., and Müller, R. 2010. Guidelines for Assessment of Bone Microstructure in Rodents Using Micro–computed Tomography. Journal of Bone and Mineral Research. 25(7): 1468-1486.

Huang, Y., Van Dessel, J., Depypere, M., EzEldeen, M., Iliescu, A. A., Dos Santos, E., and Jacobs, R. 2014. Validating Cone-Beam Computed Tomography For Peri-Implant Bone Morphometric Analysis. Bone Research. 2: 14010.

Cantley, J., and Ashcroft, F. M. 2015. Q&A: Insulin Secretion and Type 2 Diabetes: Why Do β-cells Fail?. BMC Biology. 13(1): 33.

Al-Awar, A., Kupai, K., Veszelka, M., Szűcs, G., Attieh, Z., Murlasits, Z., andVarga, C. 2016. Experimental Diabetes Mellitus in Different Animal Models. Journal of Diabetes Research.

Han, X., Tao, Y. L., Deng, Y. P., Yu, J. W., Cai, J., Ren, G. F., and Jiang, G. J. 2017. Metformin Ameliorates Insulitis in STZ-Induced Diabetic Mice. PeerJ. 5: e3155.

Nurliyani, A. H. S. 2015. Kefir Properties Prepared with Goat Milk and Black Rice (Oryza sativa L.) Extract and Its Influence on the Improvement of Pancreatic β-Cells in Diabetic Rats. Emirates Journal of Food and Agriculture. 27(10): 727-735.

Malekzadeh, B. Ö., Ransjo, M.,Tengvall, P., Mladenovic, Z., andWesterlund, A. 2017. Insulin Released from Titanium Discs with Insulin Coatings—Kinetics and Biological Activity. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 105(7): 1847-1854.

Fulzele, K., Riddle, R. C., DiGirolamo, D. J., Cao, X., Wan, C., Chen, D., and Clemens, T. L. 2010. Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body Composition. Cell. 142(2): 309-319.

Rifaai, R. A., El-Tahawy, N. F., Saber, E. A., and Ahmed, R. 2012. Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab. 3(182): 2.

Movahed, A., Larijani, B., Nabipour, I., Kalantarhormozi, M., Asadipooya, K., Vahdat, K., and Bargahi, A. 2012. Reduced Serum Osteocalcin Concentrations are Associated with Type 2 Diabetes Mellitus and the Metabolic Syndrome Components in Postmenopausal Women: The Crosstalk Between Bone and Energy Metabolism. Journal of Bone and Mineral Metabolism. 30(6): 683-691.

Wei, J., Hanna, T., Suda, N., Karsenty, G., and Ducy, P. 2014. Osteocalcin Promotes β-cell Proliferation during Development and Adulthood through Gprc6a. Diabetes. 63(3): 1021-1031.

Wheater, G., Elshahaly, M., Tuck, S. P., Datta, H. K., and van Laar, J. M. 2013. The Clinical Utility of Bone Marker Measurements in Osteoporosis. Journal of Translational Medicine. 11(1): 201.

Morris, H. A., Eastell, R., Jorgensen, N. R., Cavalier, E., Vasikaran, S., Chubb, S. A. P., andMakris, K. 2017. Clinical Usefulness Of Bone Turnover Marker Concentrations In Osteoporosis. Clinicachimicaacta. 467: 34-41.

Napoli, N., Chandran, M., Pierroz, D. D., Abrahamsen, B., Schwartz, A. V., and Ferrari, S. L. 2016. Mechanisms of Diabetes Mellitus-induced Bone Fragility. Nature Reviews Endocrinology.

Zhukouskaya, V. V., Eller-Vainicher, C., Vadzianava, V. V., Shepelkevich, A. P., Zhurava, I. V., Korolenko, G. G., &Chiodini, I. 2013. Prevalence of Morphometric Vertebral Fractures in Patients with Type 1 Diabetes. Diabetes Care. DC_121355.

Starup-Linde, J., andVestergaard, P. 2016. Biochemical Bone Turnover Markers in Diabetes Mellitus—A Systematic Review. Bone. 82: 69-78.

Burch, J., Rice, S., Yang, H., Neilson, A., Stirk, L., Francis, R., and Craig, D. 2014. Systematic Review of the Use of Bone Turnover Markers for Monitoring the Response to Osteoporosis Treatment: The Secondary Prevention of Fractures, and Primary Prevention of Fractures In High-Risk Groups.

Hagiwara, K., Goto, T., Araki, M., Miyazaki, H., and Hagiwara, H. 2011. Olive Polyphenol Hydroxytyrosol Prevents Bone Loss. European Journal of Pharmacology. 662(1-3): 78-84.

Horcajada, M. N., & Offord, E. 2012. Naturally Plant-Derived Compounds: Role in Bone Anabolism. Current Molecular Pharmacology. 5(2): 205-218.

Santiago-Mora, R., Casado-Diaz, A., De Castro, M. D., and Quesada-Gomez, J. M. 2011. Oleuropein Enhances Osteoblastogenesis and Inhibits Adipogenesis: The Effect on Differentiation in Stem Cells Derived from Bone Marrow. Osteoporosis International. 22(2): 675-684.

Jiao, H., Xiao, E., and Graves, D. T. 2015. Diabetes and Its Effect on Bone and Fracture Healing. Current Osteoporosis Reports. 13(5): 327-335.

Khan, S. N., Warkhedkar, R. M., andShyam, A. K. 2015. Analysis of Bone Mineral Density of Human Bones for Strength Evaluation. Sadhana. 40(5): 1667-1679.

Jackuliak, P., and Payer, J. 2014. Osteoporosis, Fractures, and Diabetes. International Journal Of Endocrinology.

Ma, R., Wang, L., Zhao, B., Liu, C., Liu, H., Zhu, R., and Li, Y. 2017. Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats. Cellular Physiology and Biochemistry. 41(1): 55-66.

Harvey, N. C., Glüer, C. C., Binkley, N., McCloskey, E. V., Brandi, M. L., Cooper, C., andReginster, J. Y. 2015. Trabecular Bone Score (TBS) as a New Complementary Approach for Osteoporosis Evaluation in Clinical Practice. Bone. 78: 216-224.

Topoliński, T., Cichański, A., Mazurkiewicz, A., and Nowicki, K. 2012. The Relationship between Trabecular Bone Structure Modeling Methods and the Elastic Modulus as Calculated by FEM. The Scientific World Journal.

Ma, L., Oei, L., Jiang, L., Estrada, K., Chen, H., Wang, Z., and Rivadeneira, F. 2012. Association between Bone Mineral Density and Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies. European Journal of Epidemiology. 27(5): 319-332.

Macdonald, David W., Ryan S. Squires, Shaela A. Avery, Jason Adams, Melissa Baker, Christopher R. Cunningham, Nicholas B. Heimann, David L. Kooyman, and Robert E. Seegmiller. 2013. Structural Variations in Articular Cartilage Matrix are Associated with Early-onset Osteoarthritis in the Spondyloepiphyseal Dysplasia Congenita (Sedc) Mouse. International Journal of Molecular Sciences. 14(8): 16515-16531.

Suthon, S., Jaroenporn, S., Charoenphandhu, N., Suntornsaratoon, P., andMalaivijitnond, S. 2016. Anti-osteoporotic Effects of Puerariacandollei Var. Mirifica on Bone Mineral Density and Histomorphometry in Estrogen-Deficient Rats. Journal of Natural Medicines. 70(2): 225-233.

Li, F., Yang, X., Yang, Y.,Guo, C., Zhang, C., Yang, Z., and Li, P. 2013. Antiosteoporotic Activity of Echinacoside in Ovariectomized Rats. Phytomedicine. 20(6): 549-557.




DOI: https://doi.org/10.11113/jt.v81.13681

Refbacks

  • There are currently no refbacks.


  

Copyright © 2012 Penerbit UTM Press, Universiti Teknologi Malaysia.
Disclaimer : This website has been updated to the best of our knowledge to be accurate. However, Universiti Teknologi Malaysia shall not be liable for any loss or damage caused by the usage of any information obtained from this web site.
Best viewed: Mozilla Firefox 4.0 & Google Chrome at 1024 × 768 resolution.