The effect of nobiletin on hippocampal acetylcholinesterase activity and apoptosis in amyloid beta-induced rat model of Alzheimer’s disease

Document Type : Research Paper

Authors

1 Department of Physiology, School of Medicine, Shahed University, Tehran, Iran.

2 Neurophysiology Research Center, Department of Physiology, Shahed University, Tehran, Iran

Abstract

Background and Objective: Alzheimer's disease (AD) is the most common neurodegenerative disease. Nobiletin could ameliorate acetylcholinesterase activity and apoptosis. The present study aimed to investigate the effects of nobiletin on acetylcholinesterase (AChE) activity and cell death in amyloid beta-induced model of AD in the rat.
Materials and Methods: 32 male Wistar rats were divided into four different groups as follows: sham, sham plus nobiletin, amyloid beta, and amyloid beta plus nobiletin. Rats were injected amyloid beta into the CA1 region of the hippocampus through stereotaxic surgery. Nobiletin was administered 10 mg/kg daily one hour after surgery for one week via gavage feeding. Then, apoptosis parameter (DNA fragmentation) and AChE activity were measured via separate kits in hippocampal homogenate.
Results: Our findings showed that amyloid beta group had significantly elevated level of AChE activity and DNA fragmentation as an apoptotic biomarker versus sham group (p <0.05). However, treatment of amyloid beta-microinjected rats with nobiletin non-significantly lowered hippocampal AChE activity and DNA fragmentation.
Conclusion: According to the findings of this study, AChE activity and apoptosis are increased in amyloid beta-induced model of AD and with no significant ameliorating effect of nobiletin on theses indices.

Keywords

References

  1. Gulyaeva NV, Bobkova NV, Kolosova NG, Samokhin AN, Stepanichev MY, Stefanova NA. Molecular and Cellular Mechanisms of Sporadic Alzheimer's Disease: Studies on Rodent Models in vivo. Biochemistry. Biokhimiia 2017; 82(10):1088-102.
  2. Facchinetti R, Bronzuoli MR, Scuderi C. An Animal Model of Alzheimer Disease Based on the Intrahippocampal Injection of Amyloid beta-Peptide (1-42). Methods in Molecular Biology (Clifton, N.J.) 2018; 1727:343-52.
  3. Loizzo MR, Tundis R, Bonesi M, Menichini F, De Luca D, Colica C, et al. Evaluation of Citrus aurantifolia peel and leaves extracts for their chemical composition, antioxidant and anti-cholinesterase activities. Journal of the Science of Food and Agriculture 2012; 92(15):2960-7.
  4. Kumar R, Nordberg A, Darreh-Shori T. Amyloid-beta peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAbetaACs. Brain 2016; 139(Pt 1):174-92.
  5. Obulesu M, Lakshmi MJ. Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochemical Research 2014; 39(12):2301-12.
  6. Jean YY, Baleriola J, Fa M, Hengst U, Troy CM. Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus. Journal of Visualized Experiments: Journal of Visualize Experiments 2015(100):e52805.
  7. Bolmont T, Clavaguera F, Meyer-Luehmann M, Herzig MC, Radde R, Staufenbiel M, et al. Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice. The American Journal of Pathology 2007; 171(6):2012-20.
  8. Sotthibundhu A, Sykes AM, Fox B, Underwood CK, Thangnipon W, Coulson EJ. Beta-amyloid (1-42) induces neuronal death through the p75 neurotrophin receptor. The Journal of Neuroscience 2008; 28(15):3941-6.
  9. Davydov V, Hansen LA, Shackelford DA. Is DNA repair compromised in Alzheimer's disease? Neurobiology of Aging 2003; 24(7):953-68.
  10. Schmid S, Jungwirth B, Gehlert V, Blobner M, Schneider G, Kratzer S, et al. Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test. Behavioural Brain Research 2017; 324:15-20.
  11. Braidy N, Behzad S, Habtemariam S, Ahmed T, Daglia M, Nabavi SM, et al. Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer's and Parkinson's Disease. CNS & Neurological Disorders Drug Targets 2017; 16(4):387-97.
  12. Matsuzaki K, Yamakuni T, Hashimoto M, Haque AM, Shido O, Mimaki Y, et al. Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats. Neuroscience Letters 2006; 400(3):230-4.
  13. Nakajima A, Aoyama Y, Shin EJ, Nam Y, Kim HC, Nagai T, et al. Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Abeta levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD). Behavioural Brain Research 2015; 289:69-77.
  14. Moosavi F, Hosseini R, Saso L, Firuzi O. Modulation of neurotrophic signaling pathways by polyphenols. Drug Design, Development and Therapy 2016; 10:23-42.
  15. Ellman GL, Courtney KD, Andres V, Jr., Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 1961; 7:88-95.
  16. Afshin-Majd S, Khalili M, Roghani M, Mehranmehr N, Baluchnejadmojarad T. Carnosine exerts neuroprotective effect against 6-hydroxydopamine toxicity in hemiparkinsonian rat. Molecular Neurobiology 2015; 51(3):1064-70.
  17. Tan JL, Li QX, Ciccotosto GD, Crouch PJ, Culvenor JG, White AR, et al. Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer's disease amyloid precursor protein. PloS one 2013; 8(4):e61246.
  18. Kiasalari Z, Heydarifard R, Khalili M, Afshin-Majd S, Baluchnejadmojarad T, Zahedi E, et al. Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms. Psychopharmacology 2017; 234(12):1841-52.
  19. Nakajima A, Yamakuni T, Haraguchi M, Omae N, Song SY, Kato C, et al. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice. Journal of Pharmacological Sciences 2007; 105(1):122-6.
  20. Orhan I, Kartal M, Tosun F, Sener B. Screening of various phenolic acids and flavonoid derivatives for their anticholinesterase potential. Zeitschrift fur Naturforschung. C, Journal of Biosciences 2007; 62(11-12):829-32.
  21. Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C, et al. Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer's disease: Understanding the Therapeutics Strategies. Molecular Neurobiology 2016; 53(1):648-61.
  22. Cho HW, Jung SY, Lee GH, Cho JH, Choi IY. Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide-induced oxidative stress in HT22 murine hippocampal neuronal cells. Pharmacognosy Magazine 2015; 11(Suppl 2):S284-9.
  23. Bi J, Zhang H, Lu J, Lei W. Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats. Molecular Medicine Reports 2016; 14(6):5408-14.
Journal of Basic and Clinical Pathophysiology
Volume 8, Issue 2
December 2020
Pages 44-49

Files

Share

How to cite

Statistics