Nar Çekirdeği Yağı ve Punisik Asidin Alzheimer Hastalığına Etkisi

Öz

Alzheimer hastalığı nörodejeneratif bir hastalıktır ve yaşlı nüfus ile birlikte en sık görülen senil demans vakalarından biridir. Yapılan çalışmalar Alzheimer hastası olan bireylerin sayısının 2050 yılına kadar 115,4 milyon olacağını öngörmektedir. Alzheimer hastalığının oluşumunu önlemek, yavaşlatmak ve oluşumundan sonraki semptomları hafifletmek için yeni ve alternatif yöntemlere ihtiyaç vardır. Alzheimer hastalığı gelişiminde, oksidatif hasar ve inflamasyonun anahtar rolü olduğundan, yüksek anti-oksidatif ve anti-inflamatuar özelliklere sahip fitokimyasallar, hastalığın ilerlemesinin durdurulmasına yardımcı olmak için araştırılmaktadır. Nar çekirdeği ve içeriğindeki ana bileşen olan konjuge linoleik asidin omega-5 izomeri punisik asidin anti-inflamatuar, antioksidan ve nöroprotektif özellikleri Alzheimer ve nörodejeneratif hastalıkların oluşumunda ve semptomların azaltılmasında etkili bir yol olabileceği düşünülmektedir. Bu derlemede nar çekirdeği yağı ve punisik asidin Alzheimer hastalığı üzerine etkileri ele alınmaktadır.

Anahtar Kelimeler

• Alzheimer hastalığı
• anti-inflamatuar
• nar çekirdeği yağı
• nöroprotektif
• punisik asit

Effect of Pomegranate Seed Oil and Punicic Acid on Alzheimer’s Disease

Öz

Alzheimer's disease is a neurodegenerative disease and is one of the most common forms of senile dementia observed in the elderly population. It is estimated that the number of individuals affected by Alzheimer's disease will reach 115.4 million by 2050. It is imperative that novel and alternative methods be developed to prevent and slow the onset of Alzheimer's disease, as well as to alleviate the symptoms that manifest subsequent to its onset. Given the pivotal role of oxidative damage and inflammation in the pathogenesis of Alzheimer's disease, there is a growing interest in phytochemicals with high antioxidant and anti-inflammatory properties as potential therapeutic agents for halting disease progression. The anti-inflammatory, antioxidant and neuroprotective properties of pomegranate seeds and punisic acid (the omega-5 isomer of conjugated linoleic acid, the main component of pomegranate seeds) are hypothesised to be an effective method of reducing the occurrence and symptoms of Alzheimer's and neurodegenerative diseases. This review examines the impact of pomegranate seed oil and punisic acid on Alzheimer's disease.

Anahtar Kelimeler

• Alzheimer
• anti-inflammatory
• neuroprotective
• pomegranate seed oil
• punicic acid

Kaynakça

1. Adu‐Frimpong, M., Omari‐Siaw, E., Mukhtar, Y. M., Xu, X., & Yu, J. (2018). Formulation of pomegranate seed oil: a promising approach of improving stability and health‐promoting properties. European Journal of Lipid Science and Technology, 120(12), 1800177. https://doi.org/10.1002/ejlt.201800177
2. Ahmad, F., Das, D., Kommaddi, R. P., Diwakar, L., Gowaikar, R., Rupanagudi, K. V., ... & Ravindranath, V. (2018). Isoform-specific hyperactivation of calpain-2 occurs presymptomatically at the synapse in Alzheimer’s disease mice and correlates with memory deficits in human subjects. Scientific reports, 8(1), 13119. https://doi.org/10.1038/s41598-018-31073-6
3. Akbar, M., Song, B. J., Essa, M. M., & Khan, M. A. (2015). Pomegranate: an ideal fruit for human health. International Journal of Nutrition, Pharmacology, Neurological Diseases, 5(4), 141-143. https://doi.org/10.4103/2231-0738.167506
4. Al-Sabahi, B. N., Fatope, M. O., Essa, M. M., Subash, S., Al-Busafi, S. N., Al-Kusaibi, F. S., & Manivasagam, T. (2017). Pomegranate seed oil: Effect on 3-nitropropionic acid-induced neurotoxicity in PC12 cells and elucidation of unsaturated fatty acids composition. Nutritional neuroscience, 20(1), 40-48. https://doi.org/10.1179/1476830514Y.0000000155
5. Anusree, S. S., Sindhu, G., Rani, M. P., & Raghu, K. G. (2018). Insulin resistance in 3T3-L1 adipocytes by TNF-α is improved by punicic acid through upregulation of insulin signalling pathway and endocrine function, and downregulation of proinflammatory cytokines. Biochimie, 146, 79-86. https://doi.org/10.1016/j.biochi.2017.11.014
6. Aruna, P., Venkataramanamma, D., Singh, A. K., & Singh, R. P. (2016). Health benefits of punicic acid: a review. Comprehensive Reviews in Food Science and Food Safety, 15(1), 16-27. https://doi.org/10.1111/1541-4337.12171 Bedel, H. A., Turgut, N. T., Kurtoglu, A. U., Usta, C. (2017). Effects of the Nutraceutical, Punicic Acid. Indian Journal Of Pharmaceutical Sciences, 79(3), 328-334. https://www.ijpsonline.com/articles/effects-of-nutraceutical-punicic-acid-3332.html
7. Binyamin, O., Nitzan, K., Frid, K., Ungar, Y., Rosenmann, H., & Gabizon, R. (2019). Brain targeting of 9c, 11t-Conjugated Linoleic Acid, a natural calpain inhibitor, preserves memory and reduces Aβ and P25 accumulation in 5XFAD mice. Scientific reports, 9(1), 18437. https://doi.org/10.1038/s41598-019-54971-9
8. Boroushaki, M. T., Mollazadeh, H., & Afshari, A. R. (2016). Pomegranate seed oil: A comprehensive review on its therapeutic effects. Int J Pharm Sci Res, 7(2), 430. https://doi.org/10.13040/IJPSR.0975-8232.7(2).430-42

9. Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018). Molecular actions of PPAR α in lipid metabolism and inflammation. Endocrine reviews, 39(5), 760-802. https://doi.org/10.1210/er.2018-00064
10. Caligiani, A., Bonzanini, F., Palla, G., Cirlini, M., & Bruni, R. (2010). Characterization of a potential nutraceutical ingredient: pomegranate (Punica granatum L.) seed oil unsaponifiable fraction. Plant foods for human nutrition (Dordrecht, Netherlands), 65(3), 277–283. https://doi.org/10.1007/s11130-010-0173-5.
11. Calvano, C. D., Losito, I., & Cataldi, T. (2021). Editorial to the Special Issue “Lipidomics and Neurodegenerative Diseases”. International Journal of Molecular Sciences, 22(3), 1270. https://doi.org/10.3390/ijms22031270
12. Chatzikostopoulos, T., Gialaouzidis, M., Koutoupa, A., & Tsolaki, M. (2024). The Effects of Pomegranate Seed Oil on Mild Cognitive Impairment. Journal of Alzheimer's Disease, 97(4),1961-1970. https://doi.org/10.3233/JAD-231100
13. Chen, H. H., Liu, P., Auger, P., Lee, S. H., Adolfsson, O., Rey-Bellet, L., ... & van der Brug, M. P. (2018). Calpain-mediated tau fragmentation is altered in Alzheimer’s disease progression. Scientific reports, 8(1), 16725. https://doi.org/10.1038/s41598-018-35130-y
14. Ciccone, L., Nencetti, S., Rossello, A., & Orlandini, E. (2023). Pomegranate: A Source of Multifunctional Bioactive Compounds Potentially Beneficial in Alzheimer’s Disease. Pharmaceuticals, 16(7), 1036. https://doi.org/10.3390/ph16071036
15. Dumurgier, J., & Tzourio, C. (2020). Epidemiology of neurological diseases in older adults. Revue neurologique, 176(9), 642–648. https://doi.org/10.1016/j.neurol.2020.01.356
16. Emami Kazemabad, M. J., Asgari Toni, S., Tizro, N., Dadkhah, P. A., Amani, H., Akhavan Rezayat, S., ... & Deravi, N. (2022). Pharmacotherapeutic potential of pomegranate in age-related neurological disorders. Frontiers in Aging Neuroscience, 14, 955735. https://doi.org/10.3389/fnagi.2022.955735
17. Fayaz, G., Goli, S. A. H., Kadivar, M., Valoppi, F., Barba, L., Balducci, C., ... & Nicoli, M. C. (2017). Pomegranate seed oil organogels structured by propolis wax, beeswax, and their mixture. European Journal of Lipid Science and Technology, 119(10), 1700032. https://doi.org/10.1002/ejlt.201700032
18. Frid, K., Binyamin, O., Usman, A., & Gabizon, R. (2020). Delay of gCJD aggravation in sick TgMHu2ME199K mice by combining NPC transplantation and Nano-PSO administration. Neurobiology of Aging, 95, 231-239. https://doi.org/10.1016/j.neurobiolaging.2020.07.030
19. George, N., AbuKhader, M., Al Balushi, K., Al Sabahi, B., & Khan, S. A. (2023). An insight into the neuroprotective effects and molecular targets of pomegranate (Punica granatum) against Alzheimer’s disease. Nutritional Neuroscience, 26(10), 975-996. https://doi.org/10.1080/1028415X.2022.2121092
20. Gil-Iturbe, E., Solas, M., Cuadrado-Tejedo, M., García-Osta, A., Escoté, X., Ramírez, M. J., & Lostao, M. P. (2020). GLUT12 expression in brain of mouse models of Alzheimer’s disease. Molecular Neurobiology, 57(2), 798-805. https://doi.org/10.1007/s12035-019-01743-1
21. Głuchowska, K., Pliszka, M., & Szablewski, L. (2021). Expression of glucose transporters in human neurodegenerative diseases. Biochemical and Biophysical Research Communications, 540, 8-15. https://doi.org/10.1016/j.bbrc.2020.12.067
22. Guerra-Vázquez, C. M., Martínez-Ávila, M., Guajardo-Flores, D., & Antunes-Ricardo, M. (2022). Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review. Foods (Basel, Switzerland), 11(3), 252. https://doi.org/10.3390/foods11030252
23. Hasnieza Mohd Rosli, N., Mastura Yahya, H., Shahar, S., Wahida Ibrahim, F., & Fadilah Rajab, N. (2020). Alzheimer's Disease and Functional Foods: An Insight on Neuroprotective Effect of its Combination. Pakistan journal of biological sciences : PJBS, 23(5), 575–589. https://doi.org/10.3923/pjbs.2020.575.589
24. HMDB: The Human Metabolome Database Metabocard for Punicic Acid (HMDB0030963),(Updated 2022). Available online: https://hmdb.ca/metabolites/HMDB0030963#links)
25. Holic, R., Xu, Y., Caldo, K. M. P., Singer, S. D., Field, C. J., Weselake, R. J., & Chen, G. (2018). Bioactivity and biotechnological production of punicic acid. Applied microbiology and biotechnology, 102, 3537-3549. https://doi.org/10.1007/s00253-018-8883-y
26. Jacob, J., Rajiv, P., Gopalan, R., & Lakshmanaperumalsamy, P. (2019). An overview of phytochemical and pharmacological potentials of Punica granatum L. Pharmacognosy Journal, 11(5),1167-1171. https://doi.org/10.5530/pj.2019.11.181
27. Jalal, H., Pal, M. A., Hamdani, H., Rovida, M., & Khan, N. N. (2018). Antioxidant activity of pomegranate peel and seed powder extracts. Journal of Pharmacognosy and Phytochemistry, 7(5), 992-997. https://www.phytojournal.com/archives/2018/vol7issue5/PartR/7-4-732-849.pdf
28. Jurenka, J. (2008). Therapeutic applications of pomegranate (Punica granatum L.): a review. Alternative medicine review, 13(2),128-44. https://pubmed.ncbi.nlm.nih.gov/18590349/
29. Kaseke, T., Opara, U. L., & Fawole, O. A. (2021). Effects of enzymatic pretreatment of seeds on the physicochemical properties, bioactive compounds, and antioxidant activity of pomegranate seed oil. Molecules, 26(15), 4575. https://doi.org/10.3390/molecules26154575
30. Khajebishak, Y., Payahoo, L., Alivand, M., Hamishehkar, H., Mobasseri, M., Ebrahimzadeh, V., ... & Alipour, B. (2019). Effect of pomegranate seed oil supplementation on the GLUT‐4 gene expression and glycemic control in obese people with type 2 diabetes: A randomized controlled clinical trial. Journal of cellular physiology, 234(11), 19621-19628. https://doi.org/10.1002/jcp.28561
31. Khoddami, A., Man, Y. B. C., & Roberts, T. H. (2014). Physico‐chemical properties and fatty acid profile of seed oils from pomegranate (Punica granatum L.) extracted by cold pressing. European journal of lipid science and technology, 116(5), 553-562. https://doi.org/10.1002/ejlt.201300416
32. Meerts, I. A. T. M., Verspeek-Rip, C. M., Buskens, C. A. F., Keizer, H. G., Bassaganya-Riera, J., Jouni, Z. E., ... & Van de Waart, E. J. (2009). Toxicological evaluation of pomegranate seed oil. Food and Chemical Toxicology, 47(6), 1085-1092. https://doi.org/10.1016/j.fct.2009.01.031
33. Mele, M. C., Cannelli, G., Carta, G., Cordeddu, L., Melis, M. P., Murru, E., ... & Banni, S. (2013). Metabolism of c9, t11-conjugated linoleic acid (CLA) in humans. Prostaglandins, Leukotrienes and Essential Fatty Acids, 89(2-3), 115-119. https://doi.org/10.1016/j.plefa.2013.05.005
34. Mizrahi, M., Friedman-Levi, Y., Larush, L., Frid, K., Binyamin, O., Dori, D., ... & Gabizon, R. (2014). Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD. Nanomedicine: Nanotechnology, Biology and Medicine, 10(6), 1353-1363. https://doi.org/10.1016/j.nano.2014.03.015
35. Okumuş, G., Yıldız, E., & Bayizid, A. A. (2015). Doğal antioksidan bileşikler: Nar yan ürünlerinin antioksidan olarak değerlendirilmesi. Uludağ Üniversitesi Ziraat Fakültesi Dergisi, 29(2). https://dergipark.org.tr/tr/download/article-file/228160
36. Ozben, T., & Ozben, S. (2019). Neuro-inflammation and anti-inflammatory treatment options for Alzheimer's disease. Clinical biochemistry, 72, 87–89. https://doi.org/10.1016/j.clinbiochem.2019.04.001
37. Özkan, G., Subaşı, B. G., Beştepe, S. K., & Güven, E. Ç. (2022). Sürdürülebilir gıda ve tarımsal atık yönetimi. Çevre İklim ve Sürdürülebilirlik, 23(2), 145-160.
38. Öğütcü, M., & Yılmaz, E. (2015). Comparison of the pomegranate seed oil organogels of carnauba wax and monoglyceride. Journal of Applied Polymer Science, 132(4). https://doi.org/10.1002/app.41343
39. Paul, A., & Radhakrishnan, M. (2020). Pomegranate seed oil in food industry: Extraction, characterization, and applications. Trends in Food Science & Technology, 105, 273-283. https://doi.org/10.1016/j.tifs.2020.09.014
40. Pereira de Melo, I. L., de Oliveira e Silva, A. M., Yoshime, L. T., Gasparotto Sattler, J. A., Teixeira de Carvalho, E. B., & Mancini-Filho, J. (2019). Punicic acid was metabolised and incorporated in the form of conjugated linoleic acid in different rat tissues. International Journal of Food Sciences and Nutrition, 70(4), 421-431. https://doi.org/10.1080/09637486.2018.1519528
41. Pirzadeh, M., Caporaso, N., Rauf, A., Shariati, M. A., Yessimbekov, Z., Khan, M. U., ... & Mubarak, M. S. (2021). Pomegranate as a source of bioactive constituents: A review on their characterization, properties and applications. Critical reviews in food science and nutrition, 61(6), 982-999. https://doi.org/10.1080/10408398.2020.1749825
42. Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., & Ferri, C. P. (2013). The global prevalence of dementia: a systematic review and metaanalysis. Alzheimer's & dementia : the journal of the Alzheimer's Association, 9(1), 63–75.e2. https://doi.org/10.1016/j.jalz.2012.11.007
43. Sarkaki, A., Farbood, Y., Hashemi, S., & Rad, M. R. (2015). Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion/ischemia. Avicenna journal of phytomedicine, 5(1), 43-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352532/
44. Sarkaki, A., Rezaiei, M., & Rafieirad, M. (2013). Improving active and passive avoidance memories deficits due to permanent cerebral ischemia by pomegranate seed extract in female rats. The Malaysian journal of medical sciences: MJMS, 20(2), 25-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743996/
45. Shrivas, M., Khunt, D., Shrivas, M., & Misra, M. (2023). Studies on pomegranate seed oil enriched galantamine hydrobromide microemulsion: formulation, in vitro antioxidant and neuroprotective potential. Pharmaceutical Development and Technology, 28(2), 153-163. https://doi.org/10.1080/10837450.2023.2171433
46. Szablewski, L. (2021). Brain glucose transporters: role in pathogenesis and potential targets for the treatment of Alzheimer’s disease. International Journal of Molecular Sciences, 22(15), 8142. https://doi.org/10.3390/ijms22158142
47. Topkafa, M., Kara, H., & Sherazi, S. T. H. (2015). Evaluation of the triglyceride composition of pomegranate seed oil by RP-HPLC followed by GC-MS. Journal of the American Oil Chemists' Society, 92, 791-800. https://doi.org/10.1007/s11746-015-2652-1
48. Verardo, V., Garcia-Salas, P., Baldi, E., Segura-Carretero, A., Fernandez-Gutierrez, A., & Caboni, M. F. (2014). Pomegranate seeds as a source of nutraceutical oil naturally rich in bioactive lipids. Food Research International, 65, 445-452. https://doi.org/10.1016/j.foodres.2014.04.044
49. Viuda‐Martos, M., Fernández‐López, J., & Pérez‐Álvarez, J. A. (2010). Pomegranate and its many functional components as related to human health: a review. Comprehensive reviews in food science and food safety, 9(6), 635-654. https://doi.org/10.1111/j.1541-4337.2010.00131.x
50. Wang, T., Wang, J., Hu, X., Huang, X. J., & Chen, G. X. (2020). Current understanding of glucose transporter 4 expression and functional mechanisms. World journal of biological chemistry, 11(3), 76-98. https://doi.org/10.4331/wjbc.v11.i3.76
51. Wong W. (2020). Economic burden of Alzheimer disease and managed care considerations. The American journal of managed care, 26(8 Suppl), S177–S183. https://doi.org/10.37765/ajmc.2020.88482
52. Xu, Y., Mietkiewska, E., Shah, S., Weselake, R. J., & Chen, G. (2020). Punicic acid production in Brassica napus. Metabolic Engineering, 62, 20-29. https://doi.org/10.1016/j.ymben.2020.08.011
53. Yuan, G., Sinclair, A. J., Xu, C., & Li, D. (2009). Incorporation and metabolism of punicic acid in healthy young humans. Molecular nutrition & food research, 53(10), 1336-1342. https://doi.org/10.1002/mnfr.200800520
54. Zamora-López, K., Noriega, L. G., Estanes-Hernández, A., Escalona-Nández, I., Tobón-Cornejo, S., Tovar, A. R., ... & Pérez-Monter, C. (2020). Punica granatum L.-derived omega-5 nanoemulsion improves hepatic steatosis in mice fed a high fat diet by increasing fatty acid utilization in hepatocytes. Scientific Reports, 10(1), 15229. https://doi.org/10.1038/s41598-020-71878-y