The Effect of Intralesional Propolis on Transforming Growth Factor-β (TGF-β) Expression in Tendon Healing: An Experimental Study in a Wistar Rat Model of Partial Achilles Tendon Rupture
DOI:
https://doi.org/10.37287/ijghr.v8i3.1524Keywords:
achilles tendon, immunohistochemistry, propolis, transforming growth factor-betaAbstract
Transforming growth factor-beta (TGF-β) regulates tendon repair, but dysregulated expression contributes to fibrosis. Propolis contains flavonoids and phenolics with immunomodulatory activity and may influence TGF-β signaling. This study evaluated intralesional propolis on TGF-β expression in a Wistar rat partial Achilles rupture model. A true experimental post-test only control group design was used. Male Wistar rats underwent standardized partial Achilles transection (30–40% thickness) and were randomized to: 50% propolis 0.1 mL intralesional (n=9), 0.9% NaCl 0.1 mL (n=9), or no injection (n=9). On day 35, tendons were harvested for immunohistochemistry using an IHC World–based scoring (H-score 0–300) assessed in ≥5 high-power fields by two independent raters. Interobserver agreement was moderate (κ=0.444, p<0.001). TGF-β H-score categories differed significantly among groups (Kruskal–Wallis p<0.001). The propolis group shifted toward higher expression: 88.9% (8/9) were 101–200 and 11.1% (1/9) were 51–100, whereas both comparator groups clustered at 0–50 (44.4%) and 51–100 (55.6%), with none ≥101. Intralesional 50% propolis increased TGF-β immunohistochemical expression at day 35 after partial Achilles rupture, suggesting enhanced regenerative signaling during tendon healing. Further studies should assess dose–response effects and biomechanical outcomes in vivo.
References
Aminlari, A., Stone, J., McKee, R., & others. (2021). Diagnosing Achilles Tendon Rupture with Ultrasound in Patients Treated Surgically: A Systematic Review and Meta-Analysis. The Journal of Emergency Medicine, 61, 558–567.
Bahari, H., Shahraki Jazinaki, M., Aliakbarian, M., Rashidmayvan, M., Golafrouz, H., Rahnama, I., & others. (2025). Propolis supplementation on inflammatory and oxidative stress biomarkers in adults: a systematic review and meta-analysis of randomized controlled trials. Front Nutr, 12.
Balasubramaniam, A. K., Elangovan, A., Rahman, M. A., & others. (2025). Propolis: A comprehensive review on the nature’s polyphenolic wonder. Fitoterapia, 183, 106526.
Deng, Z., Fan, T., Xiao, C., & others. (2024). TGF-β signaling in health, disease and therapeutics. Sig Transduct Target Ther, 9, 61.
El-Sakhawy, M., Salama, A., & Tohamy, H. A. S. (2023). Applications of propolis-based materials in wound healing. Arch Dermatol Res, 316(1), 61.
Firmansyah, Y., Sidharta, V. M., Wijaya, L., & Tan, S. T. (2024). Unraveling the significance of growth factors (TGF-β, PDGF, KGF, FGF, Pro Collagen, VEGF) in the dynamic of wound healing. Asian Journal of Medicine and Health, 22(3), 49–61.
Irsyam, I., Mahyudin, F., Mastutik, G., Widyawati, T., Zulhendri, F., Rahmadhany, H., & others. (2025). ???????? ???????????????? cytotoxicity evaluation of bovine hydroxyapatite--propolis composite on human mesenchymal stem cells. J Med Pharm Chem Res.
Li, H., Luo, S., Wang, H., Chen, Y., Ding, M., Lu, J., Jiang, L., Lyu, K., Huang, S., & Shi, H. (2023). The mechanisms and functions of TGF-β1 in tendon healing. Injury, 54(11), 111052.
Mansfield, K., Dopke, K., Koroneos, Z., & others. (2022). Achilles Tendon Ruptures and Repair in Athletes---a Review of Sports-Related Achilles Injuries and Return to Play. Curr Rev Musculoskelet Med, 15, 353–361.
Miller, M. D., & Thompson, S. R. (2023). Miller’s Review of Orthopaedics (1st ed.). Elsevier.
Myhrvold, S. B., Brouwer, E. F., Andresen, T. K. M., & others. (2022). Nonoperative or Surgical Treatment of Acute Achilles’ Tendon Rupture. N Engl J Med, 386, 1409–1420.
Oršolić, N., & Jazvinšćak Jembrek, M. (2022). Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer. IJMS. t, 9, 23.
Randall, L. J., Bajan, S., Tran, T. D., & others. (2025). Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts. Sci Rep, 15, 27260.
Schulze-Tanzil, G. G., Delgado Cáceres, M., Stange, R., & others. (2022). Tendon healing: a concise review on cellular and molecular mechanisms with a particular focus on the Achilles tendon. Bone & Joint Research, 11, 561–574.
Xergia, S. A., Tsarbou, C., Liveris, N. I., & others. (2023). Risk factors for Achilles tendon rupture: an updated systematic review. The Physician and Sportsmedicine, 51, 506–516.
Xiaojie, W., Banda, J., Qi, H., Chang, A. K., Bwalya, C., Chao, L., & Li, X. (2022). Scarless wound healing: current insights from the perspectives of TGF-β, KGF-1, and KGF-2. Cytokine & Growth Factor Reviews, 66, 26–37.
Yang, Z., Ge, Z., Zheng, J., & others. (2025). Surgical treatment versus conservative management for acute Achilles tendon rupture: a systematic review and meta-analysis. J Orthop Surg Res, 20, 626.
Zhou, C., Liang, T., Jiang, J., Chen, J., Chen, T., Huang, S., Chen, L., Sun, X., Chen, W., Zhu, J., Wu, S., Fan, B., Liu, C., & Zhan, X. (2023). MMP9 and STAT1 are biomarkers of the change in immune infiltration after anti-tuberculosis therapy, and the immune status can identify patients with spinal tuberculosis. International Immunopharmacology, 116(December 2022), 109588. https://doi.org/10.1016/j.intimp.2022.109588
Zhu, Y., Yan, J., Zhang, H., & Cui, G. (2023). Bone marrow mesenchymal stem cell-derived exosomes: A novel therapeutic agent for tendon-bone healing. International Journal of Molecular Medicine, 52(6), 121.
Zulhendri, F., Lesmana, R., Tandean, S., & others. (2022). Recent Update on the Anti-Inflammatory Activities of Propolis. Molecules, 27, 8473.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Indonesian Journal of Global Health Research
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
