SavedAdd your journal

Journals / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 50 Sayı: 2

HESPERIDIN AND NEURODEGENERATIVE DISEASES: NEUROPROTECTIVE EFFECTS TOWARDS ALZHEIMER’S AND PARKINSON’S

HESPERİDİN VE NÖRODEJENERATİF HASTALIKLAR: ALZHEİMER VE PARKİNSON’A YÖNELİK NÖROPROTEKTİF ETKİLER

İrem Nur Şahin Anılgan(BEYKENT ÜNİVERSİTESİ)0000-0002-5446-9467
Pages
517–528
Publication Date
2026-05-19
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

However, further research is needed to determine its bioavailability, optimal dosage, and clinical efficacy.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: This study aims to examine the neuroprotective effects of hesperidin on Alzheimer’s and Parkinson’s diseases by evaluating its roles in oxidative stress, neuroinflammation, and cellular apoptosis.
📊
Key Findings & Data:Hesperidin plays a significant role in the pathophysiology of neurodegenerative diseases due to its antioxidant and anti-inflammatory properties.
💡
Conclusion & Impact:However, further research is needed to determine its bioavailability, optimal dosage, and clinical efficacy.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Alzheimer hastalığı · hesperidin · nöroinflamasyon

Abstract

Objective: This study aims to examine the neuroprotective effects of hesperidin on Alzheimer’s and Parkinson’s diseases by evaluating its roles in oxidative stress, neuroinflammation, and cellular apoptosis. Result and Discussion: The studies investigating the effects of hesperidin on amyloid beta plaques (Aβ), dopaminergic neurons, and mitochondrial functions were examined through a comprehensive literature review. Its safety profile and side effects were also reviewed. Hesperidin plays a significant role in the pathophysiology of neurodegenerative diseases due to its antioxidant and anti-inflammatory properties. In Alzheimer’s, it reduces Aβ plaques and preserves cognitive functions, while in Parkinson’s, it supports dopaminergic neurons and improves motor functions. Current studies indicate its safety even at high doses. However, further research is needed to determine its bioavailability, optimal dosage, and clinical efficacy.

Özet

Amaç: Bu çalışma, hesperidinin Alzheimer ve Parkinson hastalıkları üzerindeki nöroprotektif etkilerini inceleyerek, oksidatif stres, nöroinflamasyon ve hücresel apoptoz üzerindeki rollerini değerlendirmeyi amaçlamaktadır. Sonuç ve Tartışma: Literatür taraması yapılarak, hesperidinin amiloid beta (Aβ) plakları, dopaminerjik nöronlar ve mitokondriyal fonksiyonlar üzerindeki etkilerini değerlendiren çalışmalar incelenmiştir. Güvenlik profili ve yan etkileri de ele alınmıştır. Hesperidin, anti-oksidan ve anti-inflamatuar özellikleriyle nörodejeneratif hastalıkların patofizyolojisinde önemli bir rol oynar. Alzheimer hastalığında Aβ plaklarını azaltarak bilişsel işlevleri korurken, Parkinson hastalığında dopaminerjik nöronları destekleyerek motor fonksiyonları iyileştirir. Mevcut çalışmalar, yüksek dozlarda bile güvenli olduğunu göstermektedir. Ancak, biyoyararlanımı, optimal dozajı ve klinik etkinliği üzerine daha fazla araştırmaya ihtiyaç vardır.

🔖

Cite This Article

Anılgan, İ. N. Ş. (2026). HESPERIDIN AND NEURODEGENERATIVE DISEASES: NEUROPROTECTIVE EFFECTS TOWARDS ALZHEIMER’S AND PARKINSON’S. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 50 Sayı: 2, 517–528. https://doi.org/10.33483/jfpau.1629547

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (47)

  1. Li, X., Feng, X., Sun, X., et al. (2022). Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2019. Frontiers in Aging Neuroscience, 14, 937486. [CrossRef]
  2. Bloem, B.R., Okun, M.S., Klein, C. (2021). Parkinson’s disease. The Lancet, 397, 2284-2303. [CrossRef]
  3. Yıldırım, E.R., Güzeldemirci, N.U. (2023). Recent advances of cholinesterase inhibitors playing a critical role in the treatment of Alzheimer’s disease (2020-2022). Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 6, 197-209. [CrossRef]
  4. Zhang, Y., Chen, H., Li, R., et al. (2023). Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future. Signal Transduction and Targeted Therapy, 8, 248. [CrossRef]
  5. Hasan, S., Khatri, N., Rahman, Z.N., et al. (2023). Neuroprotective potential of flavonoids in brain disorders. Brain Sciences, 13, 1258. [CrossRef]
  6. Liu, S., Dai, H., Wang, R., et al. (2024). Dietary flavonoids: Role in preventing neurodegenerative diseases caused by brain aging by modulating the gut microbiota. Food Bioscience, 61, 104965. [CrossRef]
  7. Ayaz, M., Sadiq, A., Junaid, M., et al. (2019). Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders. Frontiers in Aging Neuroscience, 11, 155. [CrossRef]
  8. Kopalli, S.R., Behl, T., Kyada, A., et al. (2025). Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression. Neuroscience, 569, 161-183. [CrossRef]
  9. Solanki, I., Parihar, P., Parihar, M.S. (2016). Neurodegenerative diseases: From available treatments to prospective herbal therapy. Neurochemistry International, 95, 100-108. [CrossRef]
  10. Parhiz, H., Roohbakhsh, A., Soltani, F., et al. (2015). Antioxidant and anti‐inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models. Phytotherapy Research, 29, 323-331. [CrossRef]
  11. Kuşi, M., Becer, E., Vatansever, H.S. (2025). Basic approach on the protective effects of hesperidin and naringin in Alzheimer’s disease. Nutritional Neuroscience, 28, 550-562. [CrossRef]
  12. Scoditti, E. (2020). Neuroinflammation and neurodegeneration: The promising protective role of the citrus flavanone hesperetin. Nutrients, 12, 2336. [CrossRef]
  13. Hannan, M.A., Dash, R., Sohag, A.A.M., et al. (2020). Neuroprotection against oxidative stress: Phytochemicals targeting TrkB signaling and the Nrf2-ARE antioxidant system. Frontiers in Molecular Neuroscience, 13, 116. [CrossRef]
  14. Garg, A., Garg, S., Zaneveld, L., et al. (2001). Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytotherapy Research, 15, 655-669. [CrossRef]
  15. Li, X., Huang, W., Tan, R., et al. (2023). The benefits of hesperidin in central nervous system disorders, based on the neuroprotective effect. Biomedicine & Pharmacotherapy, 159, 114222. [CrossRef]
  16. Hajialyani, M., Hosein Farzaei, M., Echeverría, J., et al. (2019). Hesperidin as a neuroprotective agent: A review of animal and clinical evidence. Molecules, 24, 648. [CrossRef]
  17. Pyrzynska, K. (2022). Hesperidin: A review on extraction methods, stability and biological activities. Nutrients, 14, 2387. [CrossRef]
  18. Wdowiak, K., Walkowiak, J., Pietrzak, R., et al. (2022). Bioavailability of hesperidin and its aglycone hesperetin compounds found in citrus fruits as a parameter conditioning the pro-health potential (neuroprotective and antidiabetic activity) mini-review. Nutrients, 14, 2647. [CrossRef]
  19. Crescenti, A., Caimari, A., Alcaide-Hidalgo, J.M., et al. (2022). Hesperidin bioavailability is increased by the presence of 2S-diastereoisomer and micronization-A randomized, crossover and double-blind clinical trial. Nutrients, 14, 2481. [CrossRef]
  20. Al-Rikabi, R., Al-Shmgani, H., Dewir, Y.H., et al. (2020). In vivo and in vitro evaluation of the protective effects of hesperidin in lipopolysaccharide-induced inflammation and cytotoxicity of cell. Molecules, 25, 478. [CrossRef]
  21. Zhang, X., Liu, Z., Huang, Y., et al. (2023). Preparation and in vitro evaluation of hesperidin nanoparticles by antisolvent recrystallization in a double homogenate system. Food Chemistry: X, 18, 100639. [CrossRef]
  22. Behera, A., Satpathy, B., Sahoo, R.K., et al. (2024). Amelioration of cognition by hesperidin-conjugated cobalt oxide nanoparticles. Scientific Reports, 14, 30748. [CrossRef]
  23. Evans, J.A., Mendonca, P., Soliman, K.F. (2022). Neuroprotective effects and therapeutic potential of the citrus flavonoid hesperetin in neurodegenerative diseases. Nutrients, 14, 2228. [CrossRef]
  24. Abd Elmaaboud, M.A., Estfanous, R.S., Atef, A., et al. (2023). Dapagliflozin/Hesperidin combination mitigates lipopolysaccharide-induced Alzheimer’s disease in rats. Pharmaceuticals, 16, 1370. [CrossRef]
  25. Chen, W.W., Zhang, X., Huang, W.J. (2016). Role of neuroinflammation in neurodegenerative diseases. Molecular Medicine Reports, 13, 3391-3396. [CrossRef]
  26. Khorasanian, A.S., Fateh, S.T., Gholami, F., et al. (2023). The effects of hesperidin supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis. Frontiers in Nutrition, 10, 1177708. [CrossRef]
  27. Morand, C., Dubray, C., Milenkovic, D., et al. (2011). Hesperidin contributes to the vascular protective effects of orange juice: A randomized crossover study in healthy volunteers. The American Journal of Clinical Nutrition, 93, 73-80. [CrossRef]
  28. Apaijit, K., Pakdeechote, P., Maneesai, P., et al. (2022). Hesperidin alleviates vascular dysfunction and remodelling in high-fat/high-fructose diet-fed rats by modulating oxidative stress, inflammation, AdipoR1, and eNOS expression. Tissue and Cell, 78, 101901. [CrossRef]
  29. Atoki, A.V., Aja, P.M., Shinkafi, T.S., et al. (2023). Hesperidin plays beneficial roles in disorders associated with the central nervous system: A review. International Journal of Food Properties, 26, 1867-1884. [CrossRef]
  30. Aggarwal, V., Tuli, H.S., Thakral, F., et al. (2020). Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Experimental Biology and Medicine, 245, 486-497. [CrossRef]
  31. Bellavite, P. (2023). Neuroprotective potentials of flavonoids: Experimental studies and mechanisms of action. Antioxidants, 12, 280. [CrossRef]
  32. Ikram, M., Muhammad, T., Rehman, S.U., et al. (2019). Hesperetin confers neuroprotection by regulating Nrf2/TLR4/NF-κB signaling in an Aβ mouse model. Molecular Neurobiology, 56, 6293-6309. [CrossRef]
  33. Jo, S.H., Kim, M.E., Cho, J.H., et al. (2019). Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways. Archives of Pharmacal Research, 42, 695-703. [CrossRef]
  34. Muhammad, T., Ikram, M., Ullah, R., et al. (2019). Hesperetin, a citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4/NF-κB signaling. Nutrients, 11, 648. [CrossRef]
  35. Han, X., Zhang, Y., Zhang, L., et al. (2025). Efficacy and molecular mechanisms of hesperidin in mitigating Alzheimer’s disease: A systematic review. European Journal of Medicinal Chemistry, 283, 117144. [CrossRef]
  36. Welbat, J.U., Naewla, S., Pannangrong, W., et al. (2020). Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat. Biochemical Pharmacology, 178, 114083. [CrossRef]
  37. Muhammad, T., Ali, T., Ikram, M., et al. (2019). Melatonin rescue oxidative stress-mediated neuroinflammation/neurodegeneration and memory impairment in scopolamine-induced amnesia mice model. Journal of Neuroimmune Pharmacology, 14, 278-294. [CrossRef]
  38. Zhu, X., Liu, H., Deng, Z., et al. (2023). Hesperidin exerts anxiolytic-like effects in rats with streptozotocin-induced diabetes via PKA/CREB signaling. Current Molecular Pharmacology, 16, 91-100. [CrossRef]
  39. Kumar, S., Akhila, P.V., Suchiang, K. (2023). Hesperidin ameliorates amyloid-β toxicity and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans through acr-16 mediated activation of the autophagy pathway. Free Radical Biology and Medicine, 209, 366-380. [CrossRef]
  40. Luo, Y., Fan, H., Tan, X., et al. (2021). Hesperetin rescues emotional memory and synaptic plasticity deficit in aged rats. Behavioral Neuroscience, 135(6), 721-731. [CrossRef]
  41. Lee, D., Kim, N., Jeon, S.H., et al. (2022). Hesperidin improves memory function by enhancing neurogenesis in a mouse model of Alzheimer’s disease. Nutrients, 14, 3125. [CrossRef]
  42. Wang, D., Liu, L., Zhu, X., et al. (2014). Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer’s disease. Cellular and Molecular Neurobiology, 34, 1209-1221. [CrossRef]
  43. Thenmozhi, J.A., Raja, T.R.W., Manivasagam, T., et al. (2017). Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer's disease. Nutritional Neuroscience, 20, 360-368. [CrossRef]
  44. Kesh, S., Kannan, R.R., Sivaji, K., et al. (2021). Hesperidin downregulates kinases LRRK2 and GSK3β in a 6-OHDA induced Parkinson’s disease model. Neuroscience Letters, 740, 135426. [CrossRef]
  45. Antunes, M.S., Ladd, F.V.L., Ladd, A.A.B., et al. (2021). Hesperidin protects against behavioral alterations and loss of dopaminergic neurons in 6-OHDA-lesioned mice: The role of mitochondrial dysfunction and apoptosis. Metabolic Brain Disease, 36, 153-167. [CrossRef]
  46. Adedara, A.O., Bressan, G.N., Santos, M.M.D., et al. (2024). Antioxidant responses driven by hesperetin and hesperidin counteract Parkinson’s disease-like phenotypes in Drosophila melanogaster. NeuroToxicology, 101, 117-127. [CrossRef]
  47. Ishola, I.O., Afolayan, O., Odutola, I.O., et al. (2021). Therapeutic potential of hesperidin in Parkinson’s disease with dementia: Inhibition of alpha synuclein and amyloid beta in Drosophila melanogaster. Nigerian Journal of Physiological Sciences, 36(1), 43-48. [CrossRef]