Main Article Content
This study aimed to determine the effect of an ethanolic extract of Salvia hispanica (Sh) seeds on osteoporosis induced by methylprednisolone (MP) in female rabbits by assessing the bone mineral density (BMD), serum levels of calcium, phosphorus, vitamin D, and parathyroid hormone, as well as histopathological changes in the femur bone. Fifty female rabbits (Lepus cuniculus) averaging 1800±125 g and 8±1.4 months old were used in this study. They were randomly allocated to five groups of 10 rabbits each. The negative control group received only subcutaneous normal saline (1 mL/kg BW). The positive control group received MP subcutaneously at a dose of 0.2 mg/kg BW per day for 30 days, followed by oral normal saline (1 mL/kg BW) per day for two months. Group 3 received MP followed by oral administration of Sh seed ethanolic extract at a dose of 600 mg/kg BW per day for two months. Group 4 received MP followed by oral administration of alendronate (Ale) at a dose of 3.6 mg/kg weekly for two months. Group 5 received MP followed by Ale and then Sh seed ethanolic extract. The study continued until one week after the cessation of the treatments. The results showed that the BMD and serum concentrations of calcium, phosphorus, and vitamin D significantly decreased (P<0.05), while serum concentrations of parathyroid hormone significantly increased (P<0.05) in the positive control and alendronate groups compared with the negative control group after two months of treatment and after one week of withdrawal. However, the administration of Sh methanolic extract to the animals in the three treatment groups ameliorated these parameters and reverted them to normal values. Histopathological analysis of the femur bone head revealed abnormal bone morphology in the positive control group, while Sh extract treatment preserved the normal histology in the other groups. These findings concluded to that Sh seeds ethanolic extract has the potential to prevent bone loss induced by chronic glucocorticoid therapy and may have significant implications for the treatment of osteoporosis.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Rizzoli R, Biver E. Glucocorticoid-induced osteoporosis: who to treat with what agent? Nat Rev Rheumatol. 2015;11:98-109.
Hartmann K, Koenen M, Schauer S, Wittig-Blaich S, Ahmad M, Baschant U. Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy. Physiol Rev. 2016;96:409-447.
Al-Rekabi F, Al-Joubouri Z, Al-Baka'a H. The effect of sub-acute exposure of prednisolone in liver and kidney functions in males albino rats. Kufa Med J. 2009;12(1):394-400.
Patschan D, Loddenkemper K, Buttgereit F. Molecular mechanisms of glucocorticoid-induced osteoporosis. Bone. 2001;29(6):498-505.
Uda Y, Azab E, Sun N, Shi C, Pajevic PD. Osteocyte mechanobiology. Curr Osteoporos Rep. 2017;15(4):318-325.
Obaid AH. Prevention and treatment of Osteoporosis, An application of the Institute of Medicine (IOM) continuum of care model. Baghdad Med J Stud. 2022;2(1):1-7.
bbass SA, Ali SH. The Beneficial Role of some bone markers in evaluating women with osteoporosis under different therapeutic regimens. Iraqi J Pharm Sci. 2011;20(1):1-7.
Siris ES, Selby PL, Saag KG, Borgstrom F, Herings RM, Silverman SL. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med. 2009;122(Suppl 2):S3-13.
de Nijs RN, Jacobs JW, Lems WF, Laan RF, Algra A, Huisman AM. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med. 2006;355:675-684.
Jacobs JW, de Nijs RN, Lems WF, Geusens PP, Laan RF, Huisman AM. Prevention of glucocorticoid-induced osteoporosis with alendronate or alfacalcidol: relations of change in bone mineral density, bone markers, and calcium homeostasis. J Rheumatol. 2007;34:1051-1057.
Hoes JN, Jacobs JW, Hulsmans HM, De Nijs RN, Lems WF, Bruyn GA. High incidence rate of vertebral fractures during chronic prednisone treatment, in spite of bisphosphonate or alfacalcidol use. Extension of the alendronate or alfacalcidol in glucocorticoid-induced osteoporosis-trial. Clin Exp Rheumatol. 2010;28:354-359.
Pozzi S. Bisphosphonate associated osteonecrosis of the jaw: a review of 35 cases and an evaluation of its frequency in multiple myeloma patients. Leuk Lynphoma. 2007;48:1852-1854.
Hoff AO. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23:826-836.
Gazem RA, Sharada AC. Pharmacological properties of Salvia hispanica (Chia) seeds: A review. J Crit Rev. 2016;3(3):2394-2399.
Melo D, Machado TB, Oliveira MB. Chia seeds: an ancient grain trending in modern human diets. Food Funct. 2019;10:3068-89.
Ixtaina VY, Martinez ML, Spotorno V, Mateo CM, Maestri DM, Diehl BWK, Nolasco SM, Tomas MC. Characterization of chia seed oils obtained by pressing and solvent extraction. J Food Compos Anal. 2011;24(2):166-174.
Salih MI, Al Dabagh FMK. Comparative analysis of some phenolic acids of in vitro and in vivo grown plant leaves of Salvia hispanica. Iraqi J Agr Sci. 2021;52(1):189-195.
Grancieri M, Martino HSD, Gonzalez de Mejia E. Chia seed (Salvia hispanica L.) as a source of proteins and bioactive peptides with health benefits: a review. Compr Rev Food Sci Food Saf. 2019;18:480-99.
Oliveira-Alves SC, Vendramini-Costa DB, Betim Cazarin CB, Maróstica Júnior MR, Borges Ferreira JP, Silva AB, et al. Characterization of phenolic compounds in chia (Salvia hispanica L.) seeds, fiber flour and oil. Food Chem. 2019;16:1-21.
Valdivia-López MÁ, Tecante A. Chia (Salvia hispanica): A review of native mexican seed and its nutritional and functional properties. Adv Food Nutr Res. 2015;75:53-75.
Scapin G, Schmidt MM. Phenolics compounds, flavonoids and antioxidant activity of chia seed extracts (Salvia hispanica) obtained by different extraction conditions. Food Chem. 2019; 43:65-76.
Salim FD, Ahmed SH, Abd AM, Skben SZ, Ramadhan NAZ. Determination of total phenol, antioxidant and antimicrobial activities of Avena sativa and Ocimum basilicum. J Baghdad for Sci. 2014; 11(2): 2601- 2606.
Dugganaboyana GK, Palanisamy CP, Kiran K, Sridhar M, Velliyur KG. Dietary Evaluation, Antioxidant and Cytotoxic Activity of Crude Extract from Chia Seeds (Salvia hispanica L.) against Human Prostate Cancer Cell Line (PC3). International Journal of Pharmacognosy and Phytochemical Research. 2016; 8(8): 1358-1362.
Parsons J, Cresser M. Sulphuric –Perchloric acid digestion of plant material for the determination of nitrogen, phosphorus, potassium, calcium and magnesium. Analytica Chimica Acta. 1979; 109(2): 431-436.
Kashani IR, Moradi FM, Pasbakhsh P, Sobhani A, Nikzad H, Sobhani A. Prevention of Methylprednisolone Acetate-Induced Osteoporosis with Calcium Administration in Rat Model. Acta Medica Iranica. 2009; 474: 251-257.
Burtis CA, Edward R, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis, MO: Elsevier Saunders; 2005.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357: 266-281.
Shimizu M, Shimizu N, Tsang JC, Petroni BD, Khatri A, Potts JT, Gardella TJ. Residue 19 of the parathyroid hormone (PTH) modulates ligand interaction with the juxtamembrane region of the PTH-1 receptor. Bioch. 2002; 41:13224-13233.
Janneke C, Alers PJ, Kees J, Herman D. Effect of Bone Decalcification Procedures on DNA In Situ Hybridization and Comparative Genomic Hybridization: EDTA Is Highly Preferable to a Routinely Used Acid Decalcifier. Journal of Histochemistry and Cytochemistry. 1999; 47:703-710.
Luna LG. Manual of histological staining methods of the armed forces institute of pathology. 3rd ed. New York: McGraw-Hill; 1968.
SPSS Statistical Packages for the Social Sciences. Statistical software for windows version 24.0. Microsoft, Chicago, IL, USA. 2012.
Chang JK, Li CJ, Liao HJ, Wang CK, Wang GJ, Ho ML. Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology. 2009;258:148-156.
Eesa MJ. Histopathological study of the influence of platelet rich-plasma and low level laser therapy on healing of experimentally fractured proximal sesamoid bone in equine. Iraqi J. Vet. Med. 2017;41(1):160-168.
Wang FS, Lin CL, Chen YJ, Wang CJ, Yang KD, Huang YT, Sun YC, Huang HC. Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology. 2005;146:2415-2423.
Bartelt A, Koehne T, Tödter K, Reimer R, Müller B, Behler-Janbeck F, Heeren J, Scheja L, Niemeier A. Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase. Int. J. Mol. Sci. 2017;18:1264.
Trivedi R, Kumara S, Kumara A, Siddiquia JA, Swarnkara G, Gupta V, Kendurker A, Dwivedi AK, Romerod JR, Chattopadhyaya N. Kaempferol has osteogenic effect in ovariectomized adult Sprague–Dawley rats. Mol. Cell Endocrinol. 2008;289:85-93.
Zhu J, Tang H, Zhang Z. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs. Int Immunopharmacol. 2017;43:236-242.
Lee JW, Asai M, Jeon SK, Iimura T, Yonezawa T, Cha BY. Rosmarinic acid exerts an antiosteoporotic effect in the RANKL-induced mouse model of bone loss by promotion of osteoblastic differentiation and inhibition of osteoclastic differentiation. Mol Nutr Food Res. 2015;59:386-400.
Guo AJ, Choi RC, Zheng KY, Chen VP, Dong TT, Wang ZT, Vollmer G, Lau DT, Tsim KW. Kaempferol as a flavonoid induces osteoblastic differentiation via estrogen receptor signaling. Chin Med. 2012;7(10):43-51.
Omara EA, Shaffie NM, Et-Toumy SA, Aal WA. Histomorphometric evaluation of bone tissue exposed to experimental osteoporosis and treated with Retama Raetam extract. J Appl Sci Res. 2009;5:706-716.
Banji D, Banji OJ, Chiluka VL, Abbagoni S. Role of Triticum aestivum aqueous extract in glucocorticoid induced osteoporosis in rats. Indian J Exp Biol. 2014; 52:153-158.
Mohamad Asri SF, Mohd Ramli ES, Soelaiman IN, Mat Noh MA, Abdul Rashid AH, Suhaimi F. Piper sarmentosum effects on 11β-hydroxysteroid dehydrogenase type 1 enzyme in serum and bone in rat model of glucocorticoid-induced osteoporosis. Molecules. 2016;21:1523.
Sakhel Z F, Yahya N Z. Therapeutic Effect of Garden Cress Seed Oil (Lepidium sativum) Extract and Alendronate on Histopathology and X- Ray Changes Against Glucocorticoids-Induced Osteoporosis in Female Rabbits. Teikyo Med J. 2022;45: 5047-5054.
Turck D, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Kearney J, Maciuk, A. Safety of chia seeds (Salvia hispanica L.) as a novel food for extended uses pursuant to Regulation (EU) 2015/2283. EFSA J. 2019;17:5657.
Nicolin V, De Tommasi N, Nori SL, Costantinides F, Berton F, Di Lenarda R. Modulatory effects of plant polyphenols on bone remodeling: a prospective view from the bench to bedside. Front Endocrinol. 2019;10:494.
Da Silva BP, Toledo RCL, Grancieri M, de Castro Moreira ME, Medina NR, Silva R.R. Effects of chia (Salvia hispanica L.) on calcium bioavailability and inflammation in wistar rats. Food Res Int. 2019; 116:592-999.
Pereira da Silva B, Kolba N, Stampini MH, Hart J, Tako E. Soluble extracts from chia seed (Salvia hispanica L.) affect brush border membrane functionality, morphology and intestinal bacterial populations in vivo (Gallus gallus). Nutrients. 2019;11:2457.
Picherit C, Coxam V, Bennetau-Pelissero C. Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J. Nutr. 2000;130:1675-1681.
Ishimi Y, Yoshida M, Wakimoto S. Genistein, a soybean isoflavone, affects bone marrow lymphopoiesis and prevents bone loss in castrated male mice. Bone. 2002; 31: 180-185.
Mazziotti G, Formenti AM, Frara S, Doga M, Giustina A. Vitamin D and Glucocorticoid-Induced Osteoporosilucocors. Bilezikian JP. 2018;50:149-160.
Farhan LO, Taha EM, Farhan AM. A Case control study to determine Macrophage migration inhibitor, and Ntelopeptides of type I bone collagen Levels in the sera of osteoporosis patients. Baghdad Sci J. 2022;19(4):848-854.
An WS, Lee SM, Son YK, Kim SE, Kim KH, Han JY. Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients. Nutr Res. 2012;32(7):495-502.
Lee SM, Son YK, Kim SE, An WS. The effects of omega-3 fatty acid on vitamin D activation in hemodialysis patients: a pilot study. Mar Drugs. 2015;13(2):741-755.
Etoh M, Yamaguchi A. Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone. J Bone Miner Metab. 2010;28:641-649.
Elbahnasawy A S, Valeeva E R, El-Sayed E M, Stepanova N V. Protective effect of dietary oils containing omega-3 fatty acids against glucocorticoid-induced osteoporosis. J Nutr Health. 2019;52(4):323-331.
Ishikawa K, Nagai T, Tsuchiya K, Oshita Y, Kuroda T, Ito H, Tani S, Dodo Y, Toyone T, Inagaki K. High bone turnover status as a risk factor in symptomatic hypocalcemia following denosumab treatment in a male patient with osteoporosis. Clin Interv Aging. 2018;13:1929-1934.
Suarez-Bregua P, Guerreiro PM, Rotllant J. Stress, glucocorticoids and bone: a review from mammals and fish. Front Endocrinol. 2018;9:526.
Kohli SS, Kohli VS. Role of RANKL–RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab. 2011;15:175-181.
Varela-López A, Ochoa JJ, Llamas-Elvira JM, López-Frías M, Planells E, Speranza L. Loss of bone mineral density associated with age in male rats fed on sunflower oil is avoided by virgin olive oil intake or coenzyme Q supplementation. Int J Mol Sci. 2017;18(7):1397.
Giusti A, Hamdy NA, papapoulos SE. Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies. Bone. 2010;47:169-180.
Kumar V, Abbas A, Aster J. Robbins Basic Pathology", 10th edition, Elsevier Inc. Chapter 21, Bone, joint, soft tissue tumor. 2017;797-831.
Walsh JS. Normal bone physiology, remodelling and its hormonal regulation. Surgery (Oxford) 2015;33(1):1–6.
Elshal MF, Almalki AL, Hussein HK, Khan JA. Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in glucocorticoid-induced osteoporosis in wistar rats. Afr. J. Tradit. Complement. Altern. Med. 2013;10:267-273.
Kruger MC, Scholium LM. Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability. Prostaglandins Leukot Essent Fatty. 2005;73(5):327-334.
Montes EM, Pacheco S, Martinez GA, Freitaa MR. Long –term dietary intake of chia seed is associated with increased bone mineral content and improved hepatic and intestinal morphology in Sprague–Dawley rats. Nutrients. 2018;10(7):922-931.
El-Wakf A M, El-Komy MA, Hassan D G. Preventive effect of dried plum extract against dexamethasone-induced osteoporosis in male rats through inhibiting cathepsin-K activity, lipogenesis and trabecular bone loss. J Innov Pharm Biol Sci. 2019;6(2):52-61.