Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats

Cüneyt Çağlayan; İbrahim Bayav; Sefa Küçükler

Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats

Abstract

Introduction: Vincristine is an effective chemotherapeutic agent widely used in the treatment of hematological malignancies but is limited by its severe neurotoxic side effects. This study aimed to investigate the potential neuroprotective effects of royal jelly (RJ) on vincristine-induced neurotoxicity through modulation of the JAK2/STAT3 and mTOR/AKT/PI3K pathways in rats. Material and Method: Thirty-five male Wistar albino rats were randomly divided into five groups: Control, RJ (300 mg/kg), Vincristine (0.1 mg/kg), Vincristine + RJ150 (150 mg/kg), and Vincristine + RJ300 (300 mg/kg). Vincristine was administered intraperitoneally, while RJ was given orally via gavage. At the end of the experimental period, brain tissues were collected. Protein levels of JAK2, STAT3, mTOR, AKT, and PI3K were determined using ELISA. Results: Vincristine significantly increased JAK2 and STAT3 levels in brain tissues, whereas both RJ150 and RJ300 treatments significantly reduced these levels. Conversely, vincristine significantly decreased mTOR, AKT, and PI3K levels, which were restored upon co-treatment with RJ, particularly at the 300 mg/kg dose. Conclusion: Royal jelly demonstrated neuroprotective effects against vincristine-induced damage by regulating key components of the JAK2/STAT3 and mTOR/AKT/PI3K signaling pathways. These findings suggest that RJ may offer a promising natural adjuvant to mitigate vincristine-induced neurotoxicity. Further studies are warranted to validate these effects and elucidate the underlying mechanisms.

Keywords

References

Abdelazem, A. Z., & Abdelbaky, N. W. (2020). Royal jelly ameliorates 6-mercaptopurine induced spermatogenesis impairment and testicular apoptosis by regulating PI3K/AKT pathway in male rats.
Abdel-Hakim, A., Belal, F., Hammad, M. A., Kishikawa, N., & El-Maghrabey, M. (2025). Adoption of self-exothermic reaction for synthesis of multifunctional carbon quantum dots: Applications to vincristine sensing and cell imaging. Talanta, 282, 126971.
Ayna, A., & Darendelioğlu, E. (2022). Evaluation of the biological activities of royal jelly on prostate and breast cancer cells. Türk Doğa ve Fen Dergisi, 11(3), 166–170.
Ayna, A., Tunc, A., Özbolat, S. N., Bengü, A. Ş., Aykutoğlu, G., Canli, D., ... & Darendelioğlu, E. (2021). Anticancer, and antioxidant activities of royal jelly on HT-29 colon cancer cells and melissopalynological analysis. Turkish Journal of Botany, 45(8), 809–819.
Behranvand, N., Nasri, F., Zolfaghari Emameh, R., Khani, P., Hosseini, A., Garssen, J., & Falak, R. (2022). Chemotherapy: A double-edged sword in cancer treatment. Cancer Immunology, Immunotherapy, 71(3), 507–526.
Behranvand, N., Nasri, F., Zolfaghari Emameh, R., Khani, P., Hosseini, A., Garssen, J., & Falak, R. (2022). Chemotherapy: A double-edged sword in cancer treatment. Cancer Immunology, Immunotherapy, 71(3), 507–526.
Bengü, A. Ş., Ayna, A., Özbolat, S., Tunç, A., Aykutoğlu, G., Çiftci, M., & Darendelioğlu, E. (2020). Content and antimicrobial activities of Bingol royal jelly. Türk Tarım ve Doğa Bilimleri Dergisi, 7(2), 480–486.
Bose, S., Banerjee, S., Mondal, A., Chakraborty, U., Pumarol, J., Croley, C. R., & Bishayee, A. (2020). Targeting the JAK/STAT signaling pathway using phytocompounds for cancer prevention and therapy. Cells, 9(6), 1451.

Chen, B., Lai, J., Dai, D., Chen, R., Li, X., & Liao, N. (2019). JAK1 as a prognostic marker and its correlation with immune infiltrates in breast cancer. Aging (Albany NY), 11(23), 11124.
Cheng, Z., Li, M., Dey, R., & Chen, Y. (2021). Nanomaterials for cancer therapy: Current progress and perspectives. Journal of Hematology & Oncology, 14, 1–27. https://doi.org/10.1186/s13045-021-01096-0
Cheng, Z., Li, M., Dey, R., & Chen, Y. (2021). Nanomaterials for cancer therapy: Current progress and perspectives. Journal of Hematology & Oncology, 14, 1–27. https://doi.org/10.1186/s13045-021-01096-0
Darendelioglu, E., Caglayan, C., Küçükler, S., Bayav, İ., Kandemir, F. M., Ayna, A., & Sağ, S. (2025). 18β-glycyrrhetinic acid mitigates bisphenol A-induced liver and renal damage: Inhibition of TNF-α/NF-κB/p38-MAPK, JAK1/STAT1 pathways, oxidative stress and apoptosis. Food and Chemical Toxicology, 196, 115218.
Dodurga, Y., Elmas, L., Seçme, M., Demirkıran, N., Biray Avcı, Ç., Bağcı, G., Sağ, S., & Şatıroğlu Tufan, L. (2024). Investigation of the apoptotic and cell cycle effects of sorafenib and doxorubicin on URG4/URGCP in leukemia cells. Pamukkale Medical Journal, 17(3), 498–508. https://doi.org/10.31362/patd.1476105
Dodurga, Y., Seçme, M., Elmas, L., Demirkıran, N., Sağ, S., Adamcı, U., & Akdağ, Z. (2025). Impact of cisplatin on Kasumi-1 leukemia cell line: Gene expression and DNA damage. Pamukkale Medical Journal, 18(1), 63–71. https://doi.org/10.31362/patd.1552452
Eriten, B., Kucukler, S., Gur, C., Ayna, A., Diril, H., & Caglayan, C. (2024). Protective effects of carvacrol on mercuric chloride‐induced lung toxicity through modulating oxidative stress, apoptosis, inflammation, and autophagy. Environmental Toxicology, 39(12), 5227–5237.
Hashem, K. S., Elkelawy, A. M. M. H., Abd-Allah, S., & Helmy, N. A. (2020). Involvement of Mfn2, Bcl2/Bax signaling and mitochondrial viability in the potential protective effect of royal jelly against mitochondria-mediated ovarian apoptosis by cisplatin in rats. Iranian Journal of Basic Medical Sciences, 23(4), 515.
Herradón, E., González, C., González, A., Uranga, J. A., & López-Miranda, V. (2021). Cardiovascular toxicity induced by chronic vincristine treatment. Frontiers in Pharmacology, 12, 692970.
Ke, F., Wang, N., Zhang, X., Liu, R., Ren, T., Ke, J., ... & Ma, J. (2024). Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib. Anti-Cancer Drugs. Advance online publication.
Knoerl, R., Mazzola, E., Frazier, L., Freeman, R. L., Hammer, M., LaCasce, A., ... & Berry, D. (2025). Describing the minimally clinically important difference of a chemotherapy-induced peripheral neuropathy patient-reported outcome measure in young adults. Asia-Pacific Journal of Oncology Nursing, 100656.
Kunugi, H., & Mohammed Ali, A. (2019). Royal jelly and its components promote healthy aging and longevity: From animal models to humans. International Journal of Molecular Sciences, 20(19), 4662. https://doi.org/10.3390/ijms20194662
Lensing, M., & Jabbari, A. (2022). An overview of JAK/STAT pathways and JAK inhibition in alopecia areata. Frontiers in Immunology, 13, 955035.
Li, T., Kandula, T., Cohn, R. J., Kiernan, M. C., Park, S. B., & Farrar, M. A. (2023). Prospective assessment of vincristine-induced peripheral neuropathy in paediatric acute lymphoblastic leukemia. Clinical Neurophysiology, 154, 157–168.
Liu, S., Khan, A. R., Yang, X., Dong, B., Ji, J., & Zhai, G. (2021). The reversal of chemotherapy-induced multidrug resistance by nanomedicine for cancer therapy. Journal of Controlled Release, 335, 1–20.
Nainu, F., Masyita, A., Bahar, M. A., Raihan, M., Prova, S. R., Mitra, S., Emran, T. B., & Simal-Gandara, J. (2021). Pharmaceutical prospects of bee products: Special focus on anticancer, antibacterial, antiviral, and antiparasitic properties. Antibiotics, 10(7), 822. https://doi.org/10.3390/antibiotics10070822
Mohamed, A. A. R., Galal, A. A., & Elewa, Y. H. (2015). Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain. Acta Histochemica, 117(7), 649-658.
Rzetecka, N., Matuszewska, E., Plewa, S., Matysiak, J., & Klupczynska-Gabryszak, A. (2024). Bee products as valuable nutritional ingredients: Determination of broad free amino acid profiles in bee pollen, royal jelly, and propolis. Journal of Food Composition and Analysis, 126, 105860.
Salama, S., Shou, Q., Abd El-Wahed, A. A., Elias, N., Xiao, J., Swillam, A., ... & El-Seedi, H. R. (2022). Royal jelly: Beneficial properties and synergistic effects with chemotherapeutic drugs with particular emphasis in anticancer strategies. Nutrients, 14(19), 4166. https://doi.org/10.3390/nu14194166
Scheer, M., Polak, M., Fritzsche, S., Strauss, C., Scheller, C., & Leisz, S. (2024). Nimodipine used with vincristine: Protects Schwann cells and neuronal cells from vincristine-induced cell death but increases tumor cell susceptibility. International Journal of Molecular Sciences, 25(19), 10389. https://doi.org/10.3390/ijms251910389
Škubník, J., Pavlíčková, V. S., Ruml, T., & Rimpelová, S. (2021). Vincristine in combination therapy of cancer: Emerging trends in clinics. Biology, 10(9), 849.
Valdes-Becerril, A. G., Jimenez-Rodriguez, R., Douda, J., El Filali, B., Ballardo-Rodriguez, I. C., & Romero-Ibarra, I. C. (2025). Co-encapsulation of vincristine and vitamin E in soy lecithin/hydrogenated soy lecithin liposomes. BioNanoScience, 15(1), 164.
van den Boogaard, W. M. C., Komninos, D. S. J., & Vermeij, W. P. (2022). Chemotherapy side-effects: Not all DNA damage is equal. Cancers, 14(3), 627. https://doi.org/10.3390/cancers14030627
Yang, Q.-Y., Hu, Y.-H., Guo, H.-L., Xia, Y., Zhang, Y., Fang, W.-R., Li, Y.-M., Xu, J., Chen, F., Wang, Y.-R., & Wang, T.-F. (2021). Vincristine-induced peripheral neuropathy in childhood acute lymphoblastic leukemia: Genetic variation as a potential risk factor. Frontiers in Pharmacology, 12, 771487. https://doi.org/10.3389/fphar.2021.771487
Yardim, A., Kandemir, F. M., Ozdemir, S., Kucukler, S., Comakli, S., Gur, C., & Celik, H. (2020). Quercetin provides protection against the peripheral nerve damage caused by vincristine in rats by suppressing caspase 3, NF-κB, ATF-6 pathways and activating Nrf2, Akt pathways. Neurotoxicology, 81, 137–146

Details

Primary Language

English

Subjects

Pharmaceutical Toxicology, Toxicology

Journal Section

Research Article

Authors

Cüneyt Çağlayan
0000-0001-5608-554X
Türkiye

İbrahim Bayav ^*
0000-0002-3533-3935
Türkiye

Sefa Küçükler
0000-0002-8222-5515
Türkiye

Publication Date

September 30, 2025

Submission Date

August 1, 2025

Acceptance Date

August 28, 2025

Published in Issue

Year 2025 Volume: 1 Number: 1

IZ

https://izlik.org/JA87SS54XR

Cite

RIS / Bibtex

APA

Çağlayan, C., Bayav, İ., & Küçükler, S. (2025). Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats. Anatolian Journal of Medical Sciences, 1(1), 11-17. https://izlik.org/JA87SS54XR

AMA

1.Çağlayan C, Bayav İ, Küçükler S. Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats. Anatolian Journal of Medical Sciences. 2025;1(1):11-17. https://izlik.org/JA87SS54XR

Chicago

Çağlayan, Cüneyt, İbrahim Bayav, and Sefa Küçükler. 2025. “Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats”. Anatolian Journal of Medical Sciences 1 (1): 11-17. https://izlik.org/JA87SS54XR.

EndNote

Çağlayan C, Bayav İ, Küçükler S (September 1, 2025) Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats. Anatolian Journal of Medical Sciences 1 1 11–17.

IEEE

[1]C. Çağlayan, İ. Bayav, and S. Küçükler, “Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats”, Anatolian Journal of Medical Sciences, vol. 1, no. 1, pp. 11–17, Sept. 2025, [Online]. Available: https://izlik.org/JA87SS54XR

ISNAD

Çağlayan, Cüneyt - Bayav, İbrahim - Küçükler, Sefa. “Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats”. Anatolian Journal of Medical Sciences 1/1 (September 1, 2025): 11-17. https://izlik.org/JA87SS54XR.

JAMA

1.Çağlayan C, Bayav İ, Küçükler S. Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats. Anatolian Journal of Medical Sciences. 2025;1:11–17.

MLA

Çağlayan, Cüneyt, et al. “Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats”. Anatolian Journal of Medical Sciences, vol. 1, no. 1, Sept. 2025, pp. 11-17, https://izlik.org/JA87SS54XR.

Vancouver

1.Cüneyt Çağlayan, İbrahim Bayav, Sefa Küçükler. Investigation of the Effects of Royal Jelly on Vincristine-Induced Brain Damage in Rats. Anatolian Journal of Medical Sciences [Internet]. 2025 Sep. 1;1(1):11-7. Available from: https://izlik.org/JA87SS54XR