Pharmacological and Toxicological Properties of Propolis

Öz

Propolis is a complex bee product formed by mixing resinous substances collected by honeybees from plant buds, bark, leaves, and exudates with beeswax and bee secretions. It is considered a natural defensive material due to its functions, such as structural repair within the hive, protection against microorganisms, and maintaining colony hygiene. Its chemical composition includes flavonoids, phenolic acids and their esters, terpenoids, aromatic aldehydes, essential oil components, vitamins, and minerals. This rich composition endows propolis with antioxidant, anti-inflammatory, antimicrobial, antiviral, immunomodulatory, wound-healing, and anticancer properties. However, the toxicological aspects of propolis must be carefully evaluated, just as much as their pharmacological potential. Variations in chemical composition due to geographical and botanical factors, differences resulting from extraction methods, pesticide and heavy metal contamination, contact dermatitis, allergic reactions, potential drug interactions, and the lack of clear safe dosage ranges pose significant limitations to the clinical and veterinary use of propolis. In this review, the chemical composition, pharmacological activities, toxicological risks, potential for veterinary and clinical use, and standardization issues of propolis have been evaluated considering the current literature.

Anahtar Kelimeler

• Propolis
• pharmacology
• toxicology
• bee products
• phenolic compounds
• flavonoids

Propolisin Farmakolojik ve Toksikolojik Özellikleri

Öz

Propolis, bal arıları tarafından bitkilerin tomurcuk, kabuk, yaprak ve eksudatlarından toplanan reçinemsi maddelerin balmumu ve arı salgılarıyla karıştırılması sonucu oluşan kompleks bir arı ürünüdür. Kovan içinde yapısal onarım, mikroorganizmalara karşı koruma ve koloni hijyeninin sürdürülmesi gibi işlevleri nedeniyle doğal bir savunma materyali olarak kabul edilir. Kimyasal yapısında flavonoidler, fenolik asitler ve esterleri, terpenoidler, aromatik aldehitler, uçucu yağ bileşenleri, vitaminler ve mineral maddeler bulunur. Bu zengin bileşim propolise antioksidan, antiinflamatuvar, antimikrobiyal, antiviral, immünomodülatör, yara iyileştirici ve antikanser özellikler kazandırmaktadır. Bununla birlikte propolisin farmakolojik potansiyeli kadar toksikolojik yönleri de dikkatle değerlendirilmelidir. Kimyasal bileşimdeki coğrafi ve botanik kaynaklı değişkenlik, ekstraksiyon yöntemlerinden kaynaklanan farklılıklar, pestisit ve ağır metal kontaminasyonu, kontakt dermatit, allerjik reaksiyonlar, potansiyel ilaç etkileşimleri ve güvenli doz aralıklarının net olmaması propolisin klinik ve veteriner kullanımında önemli sınırlılıklar oluşturmaktadır. Bu derlemede propolisin kimyasal bileşimi, farmakolojik aktiviteleri, toksikolojik riskleri, veteriner ve klinik kullanım potansiyeli ile standardizasyon sorunları güncel literatür ışığında değerlendirilmiştir.

Anahtar Kelimeler

• Propolis
• farmakoloji
• toksikoloji
• arı ürünleri
• fenolik bileşikler
• flavonoidler.

Kaynakça

1. [1] Kolayli, S. (2024). A Miracle Food Supplement Obtained from Beehives: Propolis. Herbs and Spices, 3. [2] Siheri, W., Alenezi, S., Tusiimire, J., & Watson, D. G. (2025). The chemical and biological properties of propolis. In Bee products–chemical and biological properties (pp. 209-269). Cham: Springer Nature Switzerland.
2. [3] Wagh, V. D. (2013). Propolis: a wonder bees product and its pharmacological potentials. Advances in Pharmacological and Pharmaceutical Sciences, 2013(1), 308249.
3. [4] Florek, J., Dybiak, P., Bartoszek, M., Grzegorzak, E., Krawczyk, O., Minas, J., ... & Harnicki, P. (2026). Propolis–therapeutic properties and application in modern medicine: A review. Quality in Sport, 50, 67635-67635.
4. [5] 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.
5. [6] Ghallab, D., Shawky, E., Mohyeldin, M., Metwally, A. M., & Ibrahim, R. S. (2025). Propolis: An update on its chemical diversity, botanical origin and biological activities. Journal of Advanced Pharmaceutical Sciences, 2(1), 76-99.
6. [7] Moreira da Fonseca Vitorino, L. L., Pena, C. C., & Boas Neves, C. V. (2024). Própolis: Propriedades E Aplicação Na Saúde Humana. Revista Foco (Interdisciplinary Studies Journal), 17(12).
7. [8] Chavda, V. P., Chaudhari, A. Z., Teli, D., Balar, P., & Vora, L. (2023). Propolis and their active constituents for chronic diseases. Biomedicines, 11(2), 259.
8. [9] Mendonça, I. C., Medeiros, M. L., Penteado, R. A., Parolia, A., & Porto, I. C. (2013). An overview of the toxic effects and allergic reactions caused by propolis. drugs, 4(7).

9. [10] Kljenak, A. (2017). Fitokemijske karakteristike i biološka aktivnost propolisa (Doctoral dissertation, University of Split. Faculty of Chemistry and Technology. University of Split. School of Medicine).
10. [11] Lustosa, S. R., Galindo, A. B., Nunes, L. C., Randau, K. P., & Rolim Neto, P. J. (2008). Própolis: atualizações sobre a química e a farmacologia. Revista Brasileira de Farmacognosia, 18, 447-454.
11. [12] Abrol, D. P., Shankar, U., Nitin, K. S., & Gowda, G. B. (2016). Honeybees and beekeeping: The global scenario. In Arthropod Diversity and Conservation in the Tropics and Sub-tropics (pp. 345-372).
12. [13] Ndlovu, Nikiwe, et al. Melissopalynological investigations of seasonal honey samples from the Greater Kruger National Park, Savanna biome of South Africa. Palynology, 2023, 47.3: 2179679.
13. [14] Papakosta, F., Graikou, K., Panou, E., Hatjina, F., Charistos, L., Brusbardis, V., ... & Chinou, I. (2025). Chemical Profiling of Latvian Propolis: Regional Variations and Botanical Origins. Molecules, 30(23), 4533.
14. [15] Kasote, D., Bankova, V., & Viljoen, A. M. (2022). Propolis: Chemical diversity and challenges in quality control. Phytochemistry Reviews, 21(6), 1887-1911.
15. [16] Pastor, K., Dolašević, S., & Nastić, N. (2025). Authentication of Propolis: Integrating Chemical Profiling, Data Analysis and International Standardization—A Review. Foods, 14(24), 4259.
16. [17] Santos-Buelga, C., & González-Paramás, A. M. (2017). Phenolic composition of propolis. In Bee products-chemical and biological properties (pp. 99-111). Cham: Springer International Publishing.
17. [18] Xu, J. (2025). Nutritional Pharmacology of Propolis: Multi-Axis Mechanisms in Antioxidant, Anti Inflammatory, and Immune-Regulatory Pathways.
18. [19] Zhang, C. P., & Hu, F. L. (2009). Flavonoids in propolis. Nat Prod Res Dev, 21(6), 1084-90.
19. [20] Rehman, M. U., Abdullah, Khan, F., & Niaz, K. (2021). Bee Propolis (Caffeic Acid Phenethyl Ester) Against Cancer. In Nutraceuticals and Cancer Signaling: Clinical Aspects and Mode of Action (pp. 83 97). Cham: Springer International Publishing.
20. [21] Tolba, M. F., Omar, H. A., Azab, S. S., Khalifa, A. E., Abdel-Naim, A. B., & Abdel-Rahman, S. Z. (2016). Caffeic acid phenethyl ester: a review of its antioxidant activity, protective effects against ischemia-reperfusion injury and drug adverse reactions. Critical reviews in food science and nutrition, 56(13), 2183-2190.
21. [22] Attia, Y. A., Abd El-Hack, M. E., Alagawany, M. M., Alyileili, S. R., Asiry, K. A., Hassan, S. S., ... & Alqurashi, S. I. (2025). Propolis. In Phytogenic and Phytochemical as Alternative Feed Additives for Animal Production (pp. 151-170). Bentham Science Publishers.
22. [23] Pierański, M. K., Kaniowski, D., & Szweda, P. (2025). Therapeutic potential of Propolis in preclinical models of cancer and infectious diseases: A review. International Journal of Molecular Sciences, 26(16), 8041.
23. [24] De Vecchi, E., & Drago, L. (2007). Propolis' antimicrobial activity: what's new?. Le infezioni in Medicina, 15(1), 7-15.
24. [25] Cvek, J., Medić-Šarić, M., Vitali, D., Vedrina-Dragojević, I., Šmit, Z., & Tomić, S. (2008). The content of essential and toxic elements in Croatian propolis samples and their tinctures. Journal of Apicultural Research, 47(1), 35–45.
25. [26] Ptak, J., Miśkiewicz, M., Noga, R., Marcinkowska, J., Herc, A., Koczkodon, K., & Krompiewski, M. (2024). Propolis in Human Health: Unraveling Chemistry, Applications, and Efficacy. Quality in Sport, 21, 54248-54248.
26. [27] Pierański, M. K., Kaniowski, D., & Szweda, P. (2025). Therapeutic potential of Propolis in preclinical models of cancer and infectious diseases: A review. International Journal of Molecular Sciences, 26(16), 8041.
27. [28] Mohd, K. S., Nafi, N. E. M., Khadar, A. S. A., Badiazaman, A. A. M., & Annisava, A. R. (2018). Propolis: Traditional uses, Phytochemical Composition and Pharmacological Properties. International Journal of Engineering & Technology, 7(4.43), 78–82.
28. [29] Dwivedi, J., Sachan, P., Wal, P., & Rai, A. K. (2023). In-depth chemistry and pharmacological potential of Propolis: A critical review of recent developments. Current Traditional Medicine
29. [30] Astiah, A. asda. (2025). Oxidative Stress And Redox-Based Interventions In Chronic Diseases: A Systematic Review. Journal of Health Research and Technology, 3(2), 260–275.
30. [31] Goel, K., Chawla, I., Malik, G., & Dhanawat, M. (2025). Oxidative Stress in Cardiovascular Disorders: Mechanisms and Therapeutic Implications. In The Role of Reactive Oxygen Species in Human Health and Disease (pp. 311-338). IGI Global Scientific Publishing.
31. [32] İzol, E., & Gülçin, İ. (2024). Natural and Powerful Antioxidant Source Propolis According to in vitro Analysis Results. Natural Antioxidants and In Vitro Antioxidant Assays; İzol, E., Yapıcı, İ., Gülçin, İ., Eds, 1-15.
32. [33] Cetin, A., Bakir, S., Ozdal, T., & Capanoglu, E. (2026). Investigation of Antioxidant Properties of Propolis Products Collected from Different Regions. International Journal of Molecular Sciences, 27(2), 1046.
33. [34] Sarıkürkcü, C. (2024). Unveiling the antioxidant secrets: Phytochemical profiling and bioactive potential of water extracts from Muğla propolis samples. Celal Bayar Üniversitesi Fen Bilimleri Dergisi, 20(4), 107-115.
34. [35] Yeşilkent, E. N., & Ceylan, H. (2023). Propolis and its therapeutic potential on wound healing. International Conference on Recent Academic Studies, 1(1), 204–209.
35. [36] Al-Ani, I., Zimmermann, S., Reichling, J., & Wink, M. (2018). Antimicrobial activities of European propolis collected from various geographic origins alone and in combination with antibiotics. Medicines, 5(1), 2.
36. [37] Jia, Y., Jiang, S., Chen, C., Lu, G., Xie, Y., Sun, X., & Huang, L. (2019). Caffeic acid phenethyl ester attenuates nuclear factor-κB-mediated inflammatory responses in Müller cells and protects against retinal ganglion cell death. Molecular medicine reports, 19(6), 4863-4871.
37. [38] Olgierd, B., Kamila, Ż., Anna, B., & Emilia, M. (2021). The pluripotent activities of caffeic acid phenethyl ester. Molecules, 26(5), 1335.
38. [39] Akyol, S., Ozturk, G., Ginis, Z., Armutcu, F., Yigitoglu, M. R., & Akyol, O. (2013). In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): Therapeutic perspectives. Nutrition and Cancer, 65(4), 515-526.
39. [40] Fosu, K. Y., Quarshie, J. T., Offei, N. A., Serwaa, A., Tuah, B., Sobo, A. K., Amon, J. N. K., Sarpong, K. A. N., & Aikins, A. R. (2024). Caffeic Acid Phenethyl Ester Suppresses Cytokine- and Chemotherapy Induced Inflammation in Triple-Negative Breast Cancer via NF-κB Signalling. Natural Product Communications, 19(11).
40. [41] Wrońska, A., & Kuna, A. (2023). Przeciwbakteryjne, przeciwgrzybicze i przeciwwirusowe działanie propolisu. Przegląd literatury. Kosmos, 72(1), 71-78.
41. [42] Al-Azzawi, M., Hadi, I., Mamdooh, I., & Al-Fahham, A. (2024). The chemical compositions and antimicrobial activity of propolis: A review article. Int. J. Health Res, 3, 535-539.
42. [43] Vilhelmova-Ilieva, N. M., Nikolova, I. N., Nikolova, N. Y., Petrova, Z. D., Trepechova, M. S., Holechek, D. I., & Tumbarski, Y. D. (2023). Antiviral potential of specially selected Bulgarian propolis extracts: in vitro activity against structurally different viruses. Life, 13(7), 1611.
43. [44] Yosri, N., Abd El-Wahed, A. A., Ghonaim, R., Khattab, O. M., Sabry, A., Ibrahim, M. A., & El-Seedi, H. R. (2021). Anti-viral and immunomodulatory properties of propolis: Chemical diversity, pharmacological properties, preclinical and clinical applications, and in silico potential against SARS CoV-2. Foods, 10(8), 1776.
44. [45] Ożarowski, M., & Karpiński, T. M. (2023). The effects of propolis on viral respiratory diseases. Molecules, 28(1), 359.
45. [46] Al Balawi, A. N., Eldiasty, J. G., Mosallam, S. A. E. R., El-Alosey, A. R., & Elmetwalli, A. (2024). Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study. Bioresources and Bioprocessing, 11(1), 108.
46. [47] Trzaskowska, Marta; Widelski, Jarosław; Okińczyk, Piotr; Kazimierczak, Paulina; Vivcharenko, Vladyslav; Przekora, Agata (2026), “Raw Data from: Targeted Screening Studies on Endemic Propolis Extracts for Selective Cytotoxicity Against Melanoma Cells”.
47. [48] Uzuner, S. Ç., Tetikoğlu, S., Birinci, E., & Adilova, A. (2019). Investigation of long-term effect of Black Sea bee’s venom on the cytotoxicity of pancreatic cancer cells. Journal of Apitherapy and Nature, 2(1), 1-6.
48. [49] Mutlu, C., Demir, Z., Özkan, A., & Erbaş, M. (2024). Phenolic changes in propolis during in vitro digestion and cytotoxic effects on human cancer cell lines. British Food Journal, 126(11), 3906-3921.
49. [50] Cho, E., Lee, J. D., & Cho, S. H. (2011). Systemic contact dermatitis from propolis ingestion. Annals of dermatology, 23(1), 85-88.
50. [51] Altabbal, S., Athamnah, K., Rahma, A., Wali, A. F., Eid, A. H., Iratni, R., & Al Dhaheri, Y. (2023). Propolis: a detailed insight of its anticancer molecular mechanisms. Pharmaceuticals, 16(3), 450.
51. [52] Zamarrenho, L. G., de Lima, M. H. F., Hori, J. I., Lima, J. A., Ambrosio, S. R., Bastos, J. K., & Berretta, A. A. (2023). Effects of three different Brazilian green propolis extract formulations on pro-and anti-inflammatory cytokine secretion by macrophages. Applied Sciences, 13(10), 6247.
52. [53] Wolska, K., Górska, A., Antosik, K., & Ługowska, K. (2019). Immunomodulatory Effects of Propolis and its Components on Basic Immune Cell Functions. Indian Journal of Pharmaceutical Sciences, 81(4).
53. [54] Loya-Hernández, L. P., Arzate-Quintana, C., Castillo-González, A. R., Camarillo-Cisneros, J., Romo-Sáenz, C. I., Favila-Pérez, M. A., & Quiñonez-Flores, C. M. (2025). Propolis-Functionalized Biomaterials for Wound Healing: A Systematic Review with Emphasis on Polysaccharide-Based Platforms. Polysaccharides, 6(3), 74.
54. [55] Manginstar, C. O., Tallei, T. E., Niode, N. J., Salaki, C. L., & Hessel, S. S. (2024). Therapeutic potential of propolis in alleviating inflammatory response and promoting wound healing in skin burn. Phytotherapy Research, 38(2), 856-879.
55. [56] Aldana-Mejia, J. A., Ccana-Ccapatinta, G. V., Squarisi, I. S., Nascimento, S., Tanimoto, M. H., Ribeiro, V. P., & Bastos, J. K. (2021). Nonclinical toxicological studies of Brazilian red propolis and its primary botanical source Dalbergia ecastaphyllum. Chemical Research in Toxicology, 34(4), 1024-1033.
56. [57] Ngo, T. L., Lee, C.-H., Han, N., Back, H., Rhee, S., Noh, K., Yun, H., Kang, W., & Chae, J. (2020). Application of an Inter-Species Extrapolation Method for the Prediction of Drug Interactions between Propolis and Duloxetine in Humans. International Journal of Molecular Sciences, 21(5), 1862.
57. [58]de Groot, A. C. (2013). Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects. Dermatitis, 24(6), 263-282.
58. [59] Kim, J. E., Shin, H., & Ro, Y. S. (2009). A case of allergic contact dermatitis to propolis on the lips and oral mucosa. Korean Journal of Dermatology, 199-202.
59. [60] Walgrave, S. E., Warshaw, E. M., & Glesne, L. A. (2005). Allergic contact dermatitis from propolis. Dermatitis, 16(4), 209-215.
60. [61] Vakhonina, E. A., Lapynina, E. P., & Lizunova, A. S. (2021, November). Study of toxic elements in propolis. In IOP Conference Series: Earth and Environmental Science (Vol. 845, No. 1, p. 012122). IOP Publishing. metals using
61. [62] Zavrtnik, S., Loborec, J., Kapelj, S., & Grčić, I. (2024). Environmental biomonitoring of heavy and toxic honeybees research. Sustainability, 16(19), 8526. and their products—An overview of previous
62. [63] Eskov, E. K., Eskova, M. D., Dubovik, V. A., & Vyrodov, I. V. (2015). Content of heavy metals in melliferous vegetation, bee bodies, and beekeeping production. Russian Agricultural Sciences, 41(5), 396–398.
63. [64] Balderrama-Carmona, A. P., Ramos-García, V., Ruiz-López, L., & Felipe-Ortega-Fonseca, X. (2024). Propolis as a bioindicator of contamination with toxic metals. In Heavy Metal Remediation: Sustainable Nexus Approach (pp. 289-317). Cham: Springer Nature Switzerland.
64. [65] Ryu, C. S., Oh, S. J., Oh, J. M., Lee, J. Y., Lee, S. Y., Chae, J. W., & Kim, S. K. (2016). Inhibition of cytochrome P450 by propolis in human liver microsomes. Toxicological research, 32(3), 207-213.
65. [66] Hossain, S., Yousaf, M., Liu, Y., Chang, D., & Zhou, X. (2022). An overview of the evidence and mechanism of drug–herb interactions between propolis and pharmaceutical drugs. Frontiers in Pharmacology, 13, 876183.
66. [67] Samuels, N. (2005). Herbal remedies and anticoagulant therapy. Thrombosis and haemostasis, 93(01), 03-07.
67. [68] dos Santos Madeiro, M. E., Steinle, E. C., de Araujo Paes-Souza, S., Treuko, S. K. M., & de Amorim Carvalho, E. J. (2024). Uso da própolis na cavidade oral em pacientes oncológicos: Uma revisão de literatura. Research, Society and Development, 13(11), e106131147462-e106131147462.
68. [69] Vieira, M. D. L. T., & Huang, S. M. (2012). Botanical-drug interactions: a scientific perspective. Planta medica, 78(13), 1400-1415.
69. [70] Abd-El-Samie, E. M., Seyam, H., El-Deeb, A., El-Mohandes, S., Badr, M. S., Surano, A., & Abou Kubaa, R. (2025). The antiviral activities of Egyptian ethanolic propolis extract and honey bee venom against honey bees infected with multiple viruses in vitro. Journal of Apicultural Research, 64(3), 848 861.
70. [71] Menniti-Ippolito, F., Mazzanti, G., Vitalone, A., Firenzuoli, F., & Santuccio, C. (2008). Surveillance of suspected adverse reactions to natural health products: the case of propolis. Drug Safety, 31(5), 419 423.