Research Article
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Effects of Bee Pollen on Alveolar Bone Loss and Inflammatory Markers in Rats with Experimental Periodontitis

Year 2025, Volume: 26 Issue: 3, 340 - 349, 22.09.2025
https://doi.org/10.69601/meandrosmdj.1690457

Abstract

Objective: This study aimed to investigate both the systemic and local anti-inflammatory effects of bee pollen in a rat model of experimental periodontitis.
Materials and Methods: A total of 24 rats were randomly divided into three experimental groups: 1) healthy (H), 2) periodontitis (P), and 3) periodontitis + bee pollen (P+BP). Experimental periodontitis was induced by placing ligatures on maxillary molars. Bee pollen was administered orally to the P+BP group for 14 days. On the 15th day of the experiment, the rats were euthanized, and jaw tissues along with serum samples were collected for biochemical, histological, histomorphometric, and immunohistochemical evaluations. Serum concentrations of IL-4 and IL-6 were determined using ELISA, while RANKL and OPG expressions were evaluated through immunohistochemical staining.
Results: Bone loss was higher in the periodontitis groups than in the healthy group, but the difference was not statistically significant (p > 0.05). There were no significant differences in serum IL-4 and IL-6 levels between the groups (p > 0.05). Immunohistochemical analysis indicated a significant increase in OPG and a decrease in RANKL expression in the P+BP group compared to the P group (p < 0.05). Histological examination also demonstrated notably less inflammation in the P+BP group than in the P group (p < 0.05).
Conclusion: Within the limitations of this study, it was determined that systemic bee pollen administration had no effect on serum IL-4 and IL-6 parameters, reduced RANKL levels, increased OPG levels, and thus may prevent alveolar bone loss due to periodontitis.

Ethical Statement

The animal experiment protocol was approved by the Bolu Abant İzzet Baysal University Animal Research Local Ethics Committee (Decision number: 2024/11)

Supporting Institution

This study was supported by Bolu Abant Izzet Baysal University Scientific Research Center (Project number: 2024-TDR-6.12.47-0005).

Project Number

Project number: 2024-TDR-6.12.47-0005

Thanks

The authors express their thanks to Dr. Meral Kekeçoğlu in the Department of Biology, Faculty of Science, University of Düzce; Düzce, Turkey, for providing bee pollen.

References

  • 1. Berezow AB, Darveau RP. Microbial shift and periodontitis. Periodontol 2000. 2011;55:36–47.
  • 2. Zhang M, Liu Y, Afzali H, Graves DT. An update on periodontal inflammation and bone loss. Front Immunol. 2024;15.
  • 3. Bozkurt F, Yetkınay Z, Berker E, Tepe E, Akkus S. Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis and rheumatoid arthritis: A preliminary report. Cytokine. 2006;35:180–5.
  • 4. Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019;11:30.
  • 5. Kantarci A, Hasturk H, Van Dyke TE. Host‐mediated resolution of inflammation in periodontal diseases. Periodontol 2000. 2006;40:144–63.
  • 6. Sheridan RA, Wang H-L, Eber R, Oh T-J. Systemic Chemotherapeutic Agents as Adjunctive Periodontal Therapy: A Narrative Review and Suggested Clinical Recommendations. J Int Acad Periodontol. 2015;17:123–34.
  • 7. de Sousa ET, de Araújo JSM, Pires AC, Lira dos Santos EJ. Local delivery natural products to treat periodontitis: a systematic review and meta-analysis. Clin Oral Investig. 2021;25:4599–619.
  • 8. Kumar M, Prakash S, Radha, Lorenzo JM, Chandran D, Dhumal S, et al. Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies. Antioxidants. 2022;11:823.
  • 9. Kosedag M, Gulaboglu M. Pollen and bee bread expressed highest anti-inflammatory activities among bee products in chronic inflammation: an experimental study with cotton pellet granuloma in rats. Inflammopharmacology. 2023;31:1967–75.
  • 10. Pascoal A, Rodrigues S, Teixeira A, Feás X, Estevinho LM. Biological activities of commercial bee pollens: Antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food and Chemical Toxicology. 2014;63:233–9.
  • 11. Yamaguchi M, Hamamoto R, Uchiyama S, Ishiyama K, Hashimoto K. Anabolic Effects of Bee Pollen Cistus ladaniferus Extract on Bone Components in the Femoral-Diaphyseal and -Metaphyseal Tissues of Rats in Vitro and in Vivo. Journal of Health Science. 2006;52:43–9.
  • 12. Khurelchuluun A, Uehara O, Paudel D, Morikawa T, Kawano Y, Sakata M, et al. Bee Pollen Diet Alters the Bacterial Flora and Antimicrobial Peptides in the Oral Cavities of Mice. Foods. 2021;10:1282.
  • 13. Kafadar IH, Güney A, Türk CY, Oner M, Silici S. Royal jelly and bee pollen decrease bone loss due to osteoporosis in an oophorectomized rat model. Eklem Hastalik Cerrahisi. 2012;23:100–5.
  • 14. Yamaguchı M. Regulatory Mechanism of Food Factors in Bone Metabolism and Prevention of Osteoporosis. YAKUGAKU ZASSHI. 2006;126:1117–37.
  • 15. Kuhr A, Popa‐Wagner A, Schmoll H, Schwahn C, Kocher T. Observations on experimental marginal periodontitis in rats. J Periodontal Res. 2004;39:101–6.
  • 16. Weinberg MA, Bral M. Laboratory animal models in periodontology. J Clin Periodontol. 1999;26:335–40.
  • 17. Grauballe MCB, Bentzen BH, Björnsson M, Moe D, Jonassen TEN, Bendtzen K, et al. The effect of spironolactone on experimental periodontitis in rats. J Periodontal Res. 2005;40:212–7.
  • 18. Altıntepe Doğan SS, Toker H, Göze ÖF. Melatonin Decreases Alveolar Bone Loss in Rats with Experimental Periodontitis and Osteoporosis: A Morphometric and Histopathologic Study. Biomedicines. 2024;12.
  • 19. Eteraf-Oskouei T, Shafiee-Khamneh A, Heshmati-Afshar F, Delazar A. Anti-inflammatory and anti-angiogenesis effect of bee pollen methanolic extract using air pouch model of inflammation. Res Pharm Sci. 2020;15:66.
  • 20. Maruyama H, Sakamoto T, Araki Y, Hara H. Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema. BMC Complement Altern Med. 2010;10:30.
  • 21. Semenoff TADV, Semenoff-Segundo A, Bosco ÁF, Nagata MJH, Garcia VG, Biasoli ER. Histometric analysis of ligature-induced periodontitis in rats: a comparison of histological section planes. Journal of Applied Oral Science. 2008;16:251–6.
  • 22. Belibasakis GN, Bostanci N. The RANKL‐OPG system in clinical periodontology. J Clin Periodontol. 2012;39:239–48.
  • 23. Algethami JS, El-Wahed AAA, Elashal MH, Ahmed HR, Elshafiey EH, Omar EM, et al. Bee Pollen: Clinical Trials and Patent Applications. Nutrients. 2022;14:2858.
  • 24. Marcaccini AM, Meschiari CA, Sorgi CA, Saraiva MCP, de Souza AM, Faccioli LH, et al. Circulating Interleukin‐6 and High‐Sensitivity C‐Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects. J Periodontol. 2009;80:594–602.
  • 25. Qing H, Desrouleaux R, Israni-Winger K, Mineur YS, Fogelman N, Zhang C, et al. Origin and Function of Stress-Induced IL-6 in Murine Models. Cell. 2020;182:372-387.e14.
  • 26. Brown AP, Dinger N, Levine BS. Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci. 2000;39:17–21.
  • 27. Denisow B, Denisow‐Pietrzyk M. Biological and therapeutic properties of bee pollen: a review. J Sci Food Agric. 2016;96:4303–9.
  • 28. te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990;76:1392–7.

Arı Poleninin Deneysel Periodontitisli Sıçanlarda Alveolar Kemik Kaybı ve Enflamatuar Belirteçler Üzerindeki Etkileri

Year 2025, Volume: 26 Issue: 3, 340 - 349, 22.09.2025
https://doi.org/10.69601/meandrosmdj.1690457

Abstract

Amaç: Bu çalışmanın amacı, deneysel periodontitiste arı poleninin sistemik ve lokal anti-inflamatuar etkinliğini değerlendirmektir.
Gereç ve Yöntemler: Yirmi dört sıçan rastgele üç gruba ayrıldı: 1) periodontal sağlıklı (H), 2) deneysel periodontitis (P) ve 3) deneysel periodontitis + arı poleni (P+BP). Deneysel periodontitis, maksiller molarlara ligatürler yerleştirilerek oluşturuldu. Arı poleni, P+BP grubuna 14 gün boyunca oral yoldan verildi. 15. günde sıçanlar ötanazi edildi ve biyokimyasal, histolojik, histomorfometrik ve immünohistokimyasal analizler için çene ve serum örnekleri toplandı. Serum IL-4 ve IL-6 düzeyleri ELISA ile ölçülürken, RANKL ve OPG ekspresyonu immün boyama ile değerlendirildi.
Bulgular: Kemik kaybı periodontitis gruplarında sağlıklı gruba göre daha yüksekti, ancak fark istatistiksel olarak anlamlı değildi (p > 0,05). Serum IL-4 ve IL-6 düzeyleri gruplar arasında anlamlı bir şekilde farklılık göstermedi (p > 0,05). İmmünohistokimya, P+BP grubunda P grubuna kıyasla anlamlı şekilde daha yüksek OPG ve daha düşük RANKL düzeyleri gösterdi (p < 0,05). Histopatolojik bulgular, P+BP grubunda P grubuna kıyasla anlamlı şekilde daha az inflamasyon olduğunu ortaya koydu (p < 0,05).
Sonuç: Sonuç olarak, sistemik arı poleni uygulamasının serum IL-4 ve IL-6 parametreleri üzerinde hiçbir etkisi olmadığı, RANKL düzeylerini düşürdüğü, OPG düzeylerini artırdığı görülmüş ve bu nedenle periodontitise bağlı alveolar kemik kaybını önleyebileceği belirlendi.

Project Number

Project number: 2024-TDR-6.12.47-0005

References

  • 1. Berezow AB, Darveau RP. Microbial shift and periodontitis. Periodontol 2000. 2011;55:36–47.
  • 2. Zhang M, Liu Y, Afzali H, Graves DT. An update on periodontal inflammation and bone loss. Front Immunol. 2024;15.
  • 3. Bozkurt F, Yetkınay Z, Berker E, Tepe E, Akkus S. Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis and rheumatoid arthritis: A preliminary report. Cytokine. 2006;35:180–5.
  • 4. Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019;11:30.
  • 5. Kantarci A, Hasturk H, Van Dyke TE. Host‐mediated resolution of inflammation in periodontal diseases. Periodontol 2000. 2006;40:144–63.
  • 6. Sheridan RA, Wang H-L, Eber R, Oh T-J. Systemic Chemotherapeutic Agents as Adjunctive Periodontal Therapy: A Narrative Review and Suggested Clinical Recommendations. J Int Acad Periodontol. 2015;17:123–34.
  • 7. de Sousa ET, de Araújo JSM, Pires AC, Lira dos Santos EJ. Local delivery natural products to treat periodontitis: a systematic review and meta-analysis. Clin Oral Investig. 2021;25:4599–619.
  • 8. Kumar M, Prakash S, Radha, Lorenzo JM, Chandran D, Dhumal S, et al. Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies. Antioxidants. 2022;11:823.
  • 9. Kosedag M, Gulaboglu M. Pollen and bee bread expressed highest anti-inflammatory activities among bee products in chronic inflammation: an experimental study with cotton pellet granuloma in rats. Inflammopharmacology. 2023;31:1967–75.
  • 10. Pascoal A, Rodrigues S, Teixeira A, Feás X, Estevinho LM. Biological activities of commercial bee pollens: Antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food and Chemical Toxicology. 2014;63:233–9.
  • 11. Yamaguchi M, Hamamoto R, Uchiyama S, Ishiyama K, Hashimoto K. Anabolic Effects of Bee Pollen Cistus ladaniferus Extract on Bone Components in the Femoral-Diaphyseal and -Metaphyseal Tissues of Rats in Vitro and in Vivo. Journal of Health Science. 2006;52:43–9.
  • 12. Khurelchuluun A, Uehara O, Paudel D, Morikawa T, Kawano Y, Sakata M, et al. Bee Pollen Diet Alters the Bacterial Flora and Antimicrobial Peptides in the Oral Cavities of Mice. Foods. 2021;10:1282.
  • 13. Kafadar IH, Güney A, Türk CY, Oner M, Silici S. Royal jelly and bee pollen decrease bone loss due to osteoporosis in an oophorectomized rat model. Eklem Hastalik Cerrahisi. 2012;23:100–5.
  • 14. Yamaguchı M. Regulatory Mechanism of Food Factors in Bone Metabolism and Prevention of Osteoporosis. YAKUGAKU ZASSHI. 2006;126:1117–37.
  • 15. Kuhr A, Popa‐Wagner A, Schmoll H, Schwahn C, Kocher T. Observations on experimental marginal periodontitis in rats. J Periodontal Res. 2004;39:101–6.
  • 16. Weinberg MA, Bral M. Laboratory animal models in periodontology. J Clin Periodontol. 1999;26:335–40.
  • 17. Grauballe MCB, Bentzen BH, Björnsson M, Moe D, Jonassen TEN, Bendtzen K, et al. The effect of spironolactone on experimental periodontitis in rats. J Periodontal Res. 2005;40:212–7.
  • 18. Altıntepe Doğan SS, Toker H, Göze ÖF. Melatonin Decreases Alveolar Bone Loss in Rats with Experimental Periodontitis and Osteoporosis: A Morphometric and Histopathologic Study. Biomedicines. 2024;12.
  • 19. Eteraf-Oskouei T, Shafiee-Khamneh A, Heshmati-Afshar F, Delazar A. Anti-inflammatory and anti-angiogenesis effect of bee pollen methanolic extract using air pouch model of inflammation. Res Pharm Sci. 2020;15:66.
  • 20. Maruyama H, Sakamoto T, Araki Y, Hara H. Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema. BMC Complement Altern Med. 2010;10:30.
  • 21. Semenoff TADV, Semenoff-Segundo A, Bosco ÁF, Nagata MJH, Garcia VG, Biasoli ER. Histometric analysis of ligature-induced periodontitis in rats: a comparison of histological section planes. Journal of Applied Oral Science. 2008;16:251–6.
  • 22. Belibasakis GN, Bostanci N. The RANKL‐OPG system in clinical periodontology. J Clin Periodontol. 2012;39:239–48.
  • 23. Algethami JS, El-Wahed AAA, Elashal MH, Ahmed HR, Elshafiey EH, Omar EM, et al. Bee Pollen: Clinical Trials and Patent Applications. Nutrients. 2022;14:2858.
  • 24. Marcaccini AM, Meschiari CA, Sorgi CA, Saraiva MCP, de Souza AM, Faccioli LH, et al. Circulating Interleukin‐6 and High‐Sensitivity C‐Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects. J Periodontol. 2009;80:594–602.
  • 25. Qing H, Desrouleaux R, Israni-Winger K, Mineur YS, Fogelman N, Zhang C, et al. Origin and Function of Stress-Induced IL-6 in Murine Models. Cell. 2020;182:372-387.e14.
  • 26. Brown AP, Dinger N, Levine BS. Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci. 2000;39:17–21.
  • 27. Denisow B, Denisow‐Pietrzyk M. Biological and therapeutic properties of bee pollen: a review. J Sci Food Agric. 2016;96:4303–9.
  • 28. te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990;76:1392–7.
There are 28 citations in total.

Details

Primary Language English
Subjects Oral Medicine and Pathology
Journal Section Research Article
Authors

Senem Filiz 0009-0002-1185-0652

Nuray Ercan 0000-0002-8161-7269

Esra Ateş Yildirim 0000-0001-7029-5180

Selma Erdoğan Düzcü 0000-0001-6768-1275

Project Number Project number: 2024-TDR-6.12.47-0005
Publication Date September 22, 2025
Submission Date May 3, 2025
Acceptance Date August 1, 2025
Published in Issue Year 2025 Volume: 26 Issue: 3

Cite

EndNote Filiz S, Ercan N, Ateş Yildirim E, Erdoğan Düzcü S (September 1, 2025) Effects of Bee Pollen on Alveolar Bone Loss and Inflammatory Markers in Rats with Experimental Periodontitis. Meandros Medical And Dental Journal 26 3 340–349.