PERTANIKA JOURNAL OF TROPICAL AGRICULTURAL SCIENCE

Propolis is a resin-like compound bees produce from botanical substances mixed with their saliva and beeswax. It contains antioxidants like flavonoids and phenolic acids that promote bone healing. The promising potential of propolis in supporting bone healing has significant implications in various medical and dental fields, such as orthopedics, periodontology, orthodontics, and oral and maxillofacial surgery. This review aims to evaluate the existing body of research on the impact of propolis on bone healing. A comprehensive literature search spanning the last two decades until 2024 was conducted across reputable databases utilizing the search terms “propolis AND bone AND alveolar bone AND healing. Articles with these keywords, published in English and accessible from reputable databases like PubMed, Cochrane Library, Scopus, and Google Scholar, were included. Articles from unreliable sources, non-English publications, those without full-text access, and review articles or letters to editors were excluded. Initially, 1,974 articles were identified, and after removing duplicates and applying the inclusion and exclusion criteria, 54 articles were selected, and 31 were deemed relevant for the review. The literature indicates that propolis offers significant advantages in halting the progression of bone loss and expediting bone formation and maturation, primarily due to its antioxidant and anti-inflammatory properties. Consequently, incorporating propolis could be an effective and cost-efficient strategy for managing bone defects.

• Al-Molla, B. H., Al-Ghaban, N., & Taher, A. (2014). Immunohistochemical evaluation: The effects of propolis on osseointegration of dental implants in rabbit’s tibia. Journal of Dental Research and Review, 1(3), 123-131. https://doi.org/10.4103/2348-2915.146490

• Almeida, E. C. D., & Menezes, H. (2002). Anti-inflammatory activity of propolis extracts: A review. Journal of Venomous Animals and Toxins, 8(2), 191-212. https://doi.org/10.1590/S0104-79302002000200002

• Altan, B. A., Kara, I. M., Nalcaci, R., Ozan, F., Erdogan, S. M., Ozkut, M. M., & Inan, S. (2013). Systemic propolis stimulates new bone formation at the expanded suture: A histomorphometric study. Angle Orthodontist, 83(2), 286–291. https://doi.org/10.2319/032612-253.1

• Aral, C. A., Kesim, S., Greenwell, H., Kara, M., Çetin, A., & Yakan, B. (2015). Alveolar bone protective and hypoglycemic effects of systemic propolis treatment in experimental periodontitis and diabetes mellitus. Journal of Medicinal Food, 18(2), 195–201. https://doi.org/10.1089/jmf.2013.3137

• Ari, M. D. A., Kresnoadi, U., Azhar, I. S., Sari, N., & Riawan, W. (2023). Alveolar bone formation enhancement induced by the combination of propolis extract and bovine bone graft through SMAD3 expression and woven bone in the socket preservation (an in vivo study). Research Journal of Pharmacy and Technology, 16(10), 4805-4810. https://doi.org/10.52711/0974-360X.2023.00779

• Askari, M., Jadid Tavaf, M., Ghorbani, M., Yazdanian, M., & Moghaddam, M. M. (2024). Electrospun propolis-coated PLGA scaffold enhances the osteoinduction of mesenchymal stem cells. Current Stem Cell Research and Therapy, 19(1), 94-102. https://doi.org/10.2174/1574888X18666230330085615

• Aydin, E., Hepokur, C., Misir, S., & Yeler, H. (2018). Effects of propolis on oxidative stress in rabbits undergoing implant surgery. Cumhuriyet Dental Journal, 21(2), 136–144. https://doi.org/10.7126/cumudj.356554

• Ayyad, A., Mohamed, N., Melek, L., & Khalil, N. (2023). Effects of the combination of propolis and hydroxyapatite on bone regeneration (an experimental animal study). Alexandria Dental Journal, 48(2), 95-103. https://doi.org/10.21608/adjalexu.2022.140038.1281

• Bereket, C., Özan, F., Şener, I., Tek, M., Altunkaynak, B., Z., Semirgin, S., U., Senel, E., & Ozdemir, M. (2014). Propolis accelerates the consolidation phase in distraction osteogenesis. Journal of Craniofacial Surgery, 25(5), 1912–1916. https://doi.org/10.1097/SCS.0000000000000946

• Çolak, S., Erdil, A., & Gevrek, F. (2023). Effects of systemic Anatolian propolis administration on a rat-irradiated osteoradionecrosis model. Journal of Applied Oral Science, 31, e20230231. https://doi.org/10.1590/1678-7757-2023-0231

• El-Haskoury, R., Al-Waili, N., Kamoun, Z., Makni, M., Al-Waili, A., & Lyoussi, B. (2021). Antioxidant activity and protective effect of propolis against carbon tetrachloride-induced liver and kidney injury by modulation of oxidative parameters. Veterinary World, 14(12), 3076–3083. https://doi.org/10.14202/vetworld.2021.3076-3083

• Fauzi, A., Rasul, I., Chandha M. H., Sabir, A., Yudha, G.A.W., (2024) Effectiveness of propolis application in wound healing of third molar mandibula post odontectomy (clinical and radiographic analysis) - A comparative study. Research Square. https://doi.org/10.21203/rs.3.rs-4392913/v1

• Florez, A. I. M., Malagon, S., Ocampo, S., Leal-Marin, S., Ossa, E. A., Glasmacher, B., Garcia, C., & Pelaez-Vargas, A. (2024). In vitro evaluation of the osteogenic and antimicrobial potential of porous wollastonite scaffolds impregnated with ethanolic extracts of propolis. Frontiers in Bioengineering and Biotechnology, 12, 1321466. https://doi.org/10.3389/fbioe.2024.1321466

• Guney, A., Karaman, I., Oner, M., & Yerer, M. B. (2011) Effects of propolis on fracture healing: An experimental study. Phytotherapy Research, 25(11), 1648-1652. https://doi.org/10.1002/ptr.3470

• Handayani, B., Margaretha, M. S. A., Ridwan, R. D., & Aljunaid, M. (2021). The effect of apis mellifera propolis on RUNX-2 and ALP during remodeling of orthodontic tooth movement. Research Journal of Pharmacy and Technology, 14(5), 2363-2366. https://doi.org/10.52711/0974-360X.2021.00417

• Handayani, B., Brahmanta, A., Prameswari, N., & Syahdinda, M. R. (2021). Transforming growth factor-β expression in the tension side of orthodontic tooth movement after local administration of propolis gel extract. Biochemical and Cellular Archives, 21(1), 1859-1862.

• Ibrahim, M., Khalil, N. M, & Fahmy, R. A. (2019). Management of class II furcation defects in dogs using combination of propolis and nanobone graft. Egyptian Dental Journal, 65(4), 3365–3374. https://doi.org/10.21608/EDJ.2019.74774

• Kresnoadi, U., Rahayu, R. P., Ariani, M. D., & Soesanto, S. (2020). The potential of natural propolis extract combined with bovine bone graft in increasing heat shock protein 70 and osteocalcin on socket preservation. European Journal of Dentistry, 14(1), 031–037. https://doi.org/10.1055/s-0040-1701921

• Kresnoadi, U., Sari, N., & Laksono, H. (2023). Socket preservation using a combination of propolis extract and bovine bone graft towards the expression of receptor activator of nuclear κB ligand and osteoprogerin. Folia Medica, 65(5), 737-743. https://doi.org/10.3897/folmed.65.e95802

• Kresnoadi, U., Widjaja, J., & Laksono, H. (2021). Ethanol extract of propolis-bovine bone graft combination as a prospective candidate for socket preservation: Enhancing BMP7 and decreasing NFATc1. The Saudi Dental Journal, 33(8), 1055-1062. https://doi.org/10.1016/j.sdentj.2021.05.003

• Kuropatnicki, A. K., Szliszka E., & Krol, W. (2013). Historical aspects of propolis research in modern times. Evidence-Based Complementary and Alternative Medicine, 2013(1), 964149. https://doi.org/10.1155/2013/964149.

• Kusumawati, I., Suryono, S., & Syaify, A. (2021). The enhancement of collagen type I expression after 10% propolis-carbonated hydroxyapatite application in periodontitis-induced rabbits. Dental Journal, 54(1), 16–20. https://doi.org/10.20473/j.djmkg.v54.i1.p16-20

• Lim, Y. K., Yoo, S. Y., Jang, Y. Y,, Lee, B. C., Lee, D. S., & Kook, J. K. (2019). Anti-inflammatory and in vitro bone formation effects of Garcinia mangostana L. and propolis extracts. Food Science and Biotechnology, 29(4), 539–48. https://doi.org/10.1007/s10068-019-00697-3

• Lotfy, M. (2006). Biological activity of bee propolis in health and disease. Asian Pacific Journal of Cancer Prevention, 7(1), 22–31.

• Marcucci, M. C. (1995). Propolis: Chemical composition, biological properties and therapeutic activity. Apidologie, 26(2), 83–99. https://doi.org/10.1051/apido:19950202

• Meimandi-Parizi, A., Oryan, A., Sayahi, E., & Bigham-Sadegh, A. (2018). Propolis extract a new reinforcement material in improving bone healing: An in vivo study. International Journal of Surgery, 56, 94–101. https://doi.org/10.1016/j.ijsu.2018.06.006

• Oršolić, N., & Jembrek, M. J. (2022). Molecular and cellular mechanisms of propolis and its polyphenolic compounds against cancer. International Journal of Molecular Sciences, 23(18), 10479. https://doi: 10.3390/ijms231810479

• Pereira, Y. C. L., Issa, J. P. M., Watanabe, E., Nascimento, G. C., Iyomasa, M. M., Del Ciampo, J. O., & Ervolino E. (2018). The therapeutic use of propolis extract in alveolar bone contaminated with bacterial endotoxin. Dentistry, 8(473), 2161-1122. https://doi.org/10.4172/2161-1122.1000473

• Pileggi, R., Antony, K., Johnson, K., Zuo, J., & Holliday, L. S. (2009). Propolis inhibits osteoclast maturation. Dental Traumatology, 25(6), 584–588. https://doi.org/10.1111/j.1600-9657.2009.00821.x

• Sherif, H., El Sawa, A., & Karam, S. (2015). Effect of propolis on induced alveolar bone loss in diabetic rats. Alexandria Dental Journal, 40(2), 242–248. https://doi.org/0.21608/adjalexu.2015.59160

• Somsanith, N., Kim, Y. K., Jang, Y. S., Lee, Y. H., Yi, H. K., Jang, J. H., Kim, K. A., Bae, T. S., & Lee, M. H. (2018). Enhancing of osseointegration with propolis-loaded TiO₂ nanotubes in rat mandible for dental implants. Materials, 11(1), 61. https://doi.org/10.3390/ma11010061

• Steppe, L., Megafu, M., Tschaffon-Müller, M. E. A., Ignatius, A., & Haffner-Luntzer, M. (2023). Fracture healing research: Recent insights. Bone Reports, 19, 101686. https://doi.org/10.1016/j.bonr.2023.101686

• Suryono, Wijayanti, P., & Lastianny, S. P. (2024). The effect of carbonated hidroxyapatite-10% propolis application on open flap debridement towards transforming growth factor β1 expression. Malaysian Journal of Medicine and Health Sciences, 20(2), 45-51

• Toker, H., Ozan, F., Ozer, H., Ozdemir, H., Eren, K., & Yeler, H. (2008). A morphometric and histopathologic evaluation of the effects of propolis on alveolar bone loss in experimental periodontitis in rats. Journal of Periodontology, 79(6), 1089–1094. https://doi.org/10.1902/jop.2008.070462

• Tolay, M. M., Sacchetto, J., Massad, W. A., Airaghi, F. L., González, M., & Natera, J. E., (2024). Yungas propolis in the scavenging of vitamin B2-photogenerated ROS. Journal of Photochemistry and Photobiology A: Chemistry, 452, 115611. https://doi.org/10.1016/j.jphotochem.2024.115611

• Wimolsantirungsri, N., Makeudom, A., Louwakul, P., Sastraruji, T., Chailertvanitkul, P., Supanchart, C., & Krisanaprakornkit, S. (2018). Inhibitory effect of Thai propolis on human osteoclastogenesis. Dental Traumatology, 34(4), 237–244. https://doi.org/10.1111/edt.12401

• Wiwekowati, W., Ma’ruf, M. T., Walianto, S., Sabir, A., & Widyadharma, I. P. E. (2020). Indonesian propolis reduces malondialdehyde level and increase osteoblast cell number in alveolar bone of wistar rats with orthodontic tooth movement. Open Access Macedonian Journal of Medical Sciences, 8(A), 100-104. https://doi.org/10.3889/oamjms

• Zabaiou, N., Fouache, A., Trousson, A., Baron, S., Zellagui, A., Lahouel, M., & Lobaccaro, J. A. (2017). Biological properties of propolis extracts: Something new from an ancient product. Chemistry and Physics of Lipids, 207(Part B), 214–222. https://doi.org/10.1016/j.chemphyslip.2017.04.005

• Zohery, A. A., Meshri, S. M., Madi, M. I., Rehim, S. S. A. E., & Nour, Z. M. (2018). Egyptian propolis compared to nanohydroxyapatite graft in the treatment of class II furcation defects in dogs. Journal of Periodontology, 89(11), 1340–1350. https://doi.org/10.1002/JPER.17-0685

• Zohery, A. A., Nour, Z. M., Rehim, S. S. A. E., & Mady, M. I. (2017). Histomorphometric analysis of bone regeneration after use of propolis versus nanobone graft materials for the management of class II furcation defects in dogs. Alexandria Dental Journal, 42(2), 198–203. https://doi.org/10.21608/adjalexu.2017.57927

• Zulhendri, F., Lesmana, R., Tandean, S., Christoper, A., Chandrasekaran, K., Irsyam, I., Suwantika, A. A., Abdulah, R., & Wathoni, N. (2022). Recent update on the anti-inflammatory activities of propolis. Molecules, 27(23), 8473. https://doi.org/10.3390/molecules27238473