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Effects of a Polyherbal Mixture on Femoral and Tibial Microarchitecture in Rats with Diabetic Osteoporosis Cover

Effects of a Polyherbal Mixture on Femoral and Tibial Microarchitecture in Rats with Diabetic Osteoporosis

Open Access
|Jun 2026

References

  1. Poiana C, Capatina C: Fracture risk assessment in patients with diabetes mellitus. J Clin Densitom 2017, 20(3): 432-443.
  2. Blair M: Diabetes mellitus review. Urol Nurs 2016, 36(1).
  3. Jackuliak P, Payer J: Osteoporosis, fractures, and diabetes. Int J Endocrinol 2014(1), 820615.
  4. Prasad TN, Arjunan D, Pal R, Bhadada SK: Diabetes and Osteoporosis. Indian J Orthop. 2023, 57:209-217.
  5. International Diabetes Federation: IDF Diabetes Atlas, 11th edn. Brussels, Belgium, 2025.
  6. Rubin MR: Bone cells and bone turnover in diabetes mellitus. Curr Osteoporos Rep 2015, 13(3):186-191. https://doi.org/10.1007/s11914-015-0265-0
  7. Janghorbani M, Van Dam RM, Willett WC, Hu FB: Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007, 166(5):495–505.
  8. Martínez SB, Cenarruzabeitia NV, San Martin JE, Canelas AC: The diabetic paradox: Bone mineral density and fracture in type 2 diabetes. Endocrinol Nutr (Engl Ed) 2016, 63(9): 495–501..
  9. Lespessailles E, Chappard C, Bonnet N, Benhamou CL: Imaging techniques for evaluating bone microarchitecture. Joint Bone Spine 2006, 73(3): 254–261.
  10. Asadipooya K, Uy EM: Advanced glycation end products (AGEs), receptor for AGEs, diabetes, and bone: review of the literature. J Endocr Soc 2019, 3(10):1799-1818.
  11. Yousif AE, Aziz MY: Biomechanical analysis of the human femur bone during normal walking and standing up. IOSR J Eng 2012, 2(8):13–19.
  12. Rasmussen NH, Dal J, de Vries F, van den Bergh JP, Jensen MH, Vestergaard P: Diabetes and fractures: new evidence of atypical femoral fractures? Osteoporos Int 2020, 31(3):447–455.
  13. Barak MM: Cortical and trabecular bone modeling and implications for bone functional adaptation in the mammalian tibia. Bioengineering 2024, 11(5): 514.
  14. Ott SM: Cortical or trabecular bone: what’s the difference? Am J Nephrol 2018, 47(6): 373-375.
  15. Zhao C, Yang C, Wai STC, Zhang Y, Portillo MP, Paoli P, Wu Y, Cheang WS, Liu B, Carpéné C, Xiao J:. Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus. Crit Rev Food Sci Nutr 2019, 59(6):830–847.
  16. Upadhyay S, Dixit M: Role of polyphenols and other phytochemicals on molecular signaling. Oxid Med Cell Longev 2015, 2015:504253.
  17. Madić V, Petrović A, Jušković M, Jugović D, Djordjević L, Stojanović G, Vasiljević P: Polyherbal mixture ameliorates hyperglycemia, hyperlipidemia and histopathological changes of pancreas, kidney and liver in a rat model of type 1 diabetes. J Ethnopharmacol 2021, 265:113210.
  18. Petrović A, Madić V, Jušković M, Đorđević L, Vasiljević P: Osteoprotective effects of “antidiabetic” polyherbal mixture in type 1 diabetic rats. Acta Veterinaria 2021, 71(3).
  19. Petrović A, Madić V, Stojanović G, Zlatanović I, Zlatković B, Vasiljević P, Đorđević L: Antidiabetic effects of polyherbal mixture made of Centaurium erythraea, Cichorium intybus and Potentilla erecta. J Ethnopharmacol 2024, 319: 117032.
  20. Nguyen QN, Lee SR, Kim B, Hong JH, Jang YS, Lee DE, Pang C, Kang KS, Kim KH: Estrogenic activity of 4-hydroxy-benzoic acid from Acer tegmentosum via estrogen receptor α-dependent signaling pathways. Plants 2022, 11(23):3387.
  21. Wong SK, Chin KY, Ima-Nirwana S: Quercetin as an agent for protecting the bone: a review of the current evidence. Int J Mol Sci 2020, 21(17):6448.
  22. Chen Y, Dai F, He Y, Chen Q, Xia Q, Cheng G, Lu Y, Zhang Q: Beneficial effects of hyperoside on bone metabolism in ovariectomized mice. Biomed Pharmacother 2018, 107: 1175-1182.
  23. Qi XC, Li B, Wu WL, Liu HC, Jiang YP: Protective effect of hyperoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells. Artif Cells Nanomed Biotechnol 2020, 48(1): 377-83.
  24. Ekeuku SO, Pang KL, Chin KY: Effects of caffeic acid and its derivatives on bone: a systematic review. Drug Des Devel Ther 2021, 15: 259-75.
  25. Liu L, Mu H, Pang Y: Caffeic acid treatment augments the cell proliferation, differentiation, and calcium mineralization in the human osteoblast-like MG-63 cells. Phcog Mag 2021, 17(73).
  26. Khan MS, Khan S, Khan N, Khan AS : Dietary sources, classification, biosynthesis, and mechanism of action of flavonoids in combating oxidative stress. In: Role of flavonoids in chronic metabolic diseases: from bench to clinic. WILEY online library: Scrivener Publishing LLC 2024, 67-114.
  27. Fayeda HA, Barakata BM, Elshaerb SS, Abdel-Naim AB, Menzed ET: Antiosteoporotic activities of isoquercitrin in ovariectomized rats: role of inhibiting hypoxia inducible factor-1 alpha. Eur J Pharmacol 2019, 865:172785.
  28. Horcajada-Molteni MN, Crespy V, Coxam V, Davicco MJ, Rémésy C, Barlet JP: Rutin inhibits ovariectomy-induced osteopenia in rats. J Bone Miner Res 2000, 15:2251-8.
  29. Životić D, Životić D: Lekovito bilje u narodnoj medicini. 5th ed. In: Rijeka, Beograd, Jugoslavija: Otokar Keršovani – Rijeka 1979.
  30. OECD, 2018. Repeated dose 28-day oral toxicity study in rodents (OECD TG 407). In: Revised Guidance Document 150 on Standardized Test Guidelines for Evaluating Chemicals for Endocrine Disruption. OECD Publishing, Paris.
  31. Nair AB, Jacob S: A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016, 7(2): 27.
  32. Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ: Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-κB. Biochem Biophys Res Commun 2004, 314: 197–207.
  33. Vashishth D, Gibson G, Kimura J, Schaffler MB, Fyhrie DP: Determination of bone volume by osteocyte population. Anat Rec 2002, 267:292–295.
  34. Mody N, Parhami F, Sarafian TA, Demer LL : Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 2001, 31:509–519.
  35. El-Tantawy WH, Al Haleem ENA: Therapeutic effects of stem cell on hyperglycemia, hyperlipidemia, and oxidative stress in alloxan-treated rats. Mol Cell Biochem. 2014, 391:193-200.
  36. Tsentidis C, Gourgiotis D, Kossiva L, et al.: Higher levels of s- RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int 2016, 27: 1631-1643.
  37. Diniz SF, Amorim FPLG, Cavalcante-Neto FF, Bocca AL, Batista AC, Simm G, Silva TA: Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture. Braz J Med Biol Res 2008, 41: 373–379.
  38. Chauhan S, Sharma A, Upadhyay NK, Singh G, Lal UR, Goyal R: In-vitro osteoblast proliferation and in-vivo anti-osteoporotic activity of Bombax ceiba with quantification of Lupeol, gallic acid and β-sitosterol by HPTL C and HPLC. BMC Complement Altern Med 2018, 18.
  39. Vestergaard P, Rejnmark L, Mosekilde L: Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcif Tissue Int 2009, 84:45–55.
  40. Behera HN, Patnaik BK: Recovery from alloxan diabetes as revealed by collagen characteristics of bone, skin and tendon of Swiss Mice. Gerontology 1981, 27: 32-36.
  41. Villarino ME, Sánchez LM, Bozal CB, Ubios AM: Influence of short-term diabetes on osteocytic lacunae of alveolar bone. A histomorphometric study. Acta Odontol Latinoam 2006, 19: 23–28.
  42. Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK: Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark Insights 2016, 11: BMI-S38440.
  43. Scarpa E-S, Antonelli A, Balercia G, Sabatelli S, Maggi F, Caprioli G, Giacchetti G, Micucci M: Antioxidant, Anti-Inflammatory, Anti-Diabetic, and Pro-Osteogenic Activities of Polyphenols for the Treatment of Two Different Chronic Diseases: Type 2 Diabetes Mellitus and Osteoporosis. Biomolecules 2024, 14, 836.
  44. Wang J, Wang H: Oxidative stress in pancreatic beta cell regeneration. Oxid Med Cell Longev 2017, 2017:1930261.
  45. Kyung TW, Lee JE, Shin HH, Choi HS: Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TN F-α by inhibiting activation of NF-κB. Exp Mol Med 2008, 40:52-8.
  46. Abdelnabi H, Mohsin S: Phytochemicals in bone therapy: exploring natural alternatives for bone health. Int J Nanomedicine 2025, 20: 10831–10855.
  47. Ma P, Gu B, Ma J, Wu X, Cao J, Liu H: Glimepiride induces proliferation and differentiation of rat osteoblasts via the PI3-kinase/Akt pathway. Metabolism 2010, 59(3): 359-66.
  48. Pan MA, Tan BS, Liu HC, Gu B, Ma JL, EL, Wu X: Effects of glimepiride on proliferation, differentiation and mineralization of rat mandibular osteoblasts in hyperglycemia. Shanghai J Stomatol 2013, 22(2).
  49. Fronczek-Sokół J, Pytlik M: Effect of glimepiride on the skeletal system of ovariectomized and non-ovariectomized rats. Pharmacol Rep 2014, 66(3): 412-417.
  50. Ma P, Gu B, Xiong W, Tan B, Geng W, Li J, Liu H: Glimepiride promotes osteogenic differentiation in rat osteoblasts via the PI3K/Akt/eNOS pathway in a high glucose microenvironment. PLoS One 2014, 9(11): e112243.
  51. Nyman JS, Kalaitzoglou E, Bunn RC, Uppuganti S, Thrailkill KM, Fowlkes JL: Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes. Bone reports 2017, 7: 1-8.
  52. Yeni YN, Brown CU, Wang Z, Norman TL : The influence of bone morphology on fracture toughness of the human femur and tibia. Bone 1997, 21(5): 453-459.
  53. Choi YS, Yoon JR, Shin YB, Lee SH: The difference in bone mineral density between femur and tibia is related to tibia deformation in endstage knee osteoarthritis. The Knee 2024, 51: 173-180.
  54. Kirschner MH, Menck J, Hennerbichler A, Gaber O, Hofmann GO: Importance of arterial blood supply to the femur and tibia for transplantation of vascularized femoral diaphyses and knee joints. World J Surg 1998, 22(8): 845–852.
  55. Rask-Madsen C, and King GL: Vascular complications of diabetes: mechanisms of injury and protective factors. Cell metab 2013, 17(1): 20-33.
  56. Martin RB, and Ishida J: The relative effects of collagen fiber orientation, porosity, density, and mineralization on bone strength. J Biomech 1989, 22: 419-426.
  57. Julkunen P, Iivarinen J, Brama PA, Arokoski J, Jurvelin JS, Helminen HJ: Maturation of collagen fibril network structure in tibial and femoral cartilage of rabbits. Osteoarthritis Cartilage 2010, 18(3): 406-415.
DOI: https://doi.org/10.2478/acve-2026-0020 | Journal eISSN: 1820-7448 | Journal ISSN: 0567-8315
Language: English
Page range: 281 - 302
Submitted on: Dec 5, 2025
Accepted on: May 12, 2026
Published on: Jun 23, 2026
In partnership with: Paradigm Publishing Services
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© 2026 Bojana Maksimović, Aleksandra Petrović, Višnja Madić, Nemanja Mladenović, Bojan Zlatković, Ljubiša Đorđević, Perica Vasiljević, published by University of Belgrade, Faculty of Veterinary Medicine
This work is licensed under the Creative Commons Attribution 4.0 License.