Nörodejeneratif Hastalıkların Tedavisinde Nöroprotektif Ajan Olarak Tıbbi Bitkiler ve Fitokimyasallar

Öz

Nörodejeneratif hastalıklar, sinir hücrelerindeki yapısal ve işlevsel dejenerasyon ve/veya sinir hücrelerinin ölümü ile karakterize multifaktöryel hastalıklardır. Alzheimer, Parkinson, Huntington, Amyotrofik Lateral Skleroz ve Multiple Skleroz insanların yaşam kalitesini olumsuz yönde etkileyen ve hızlı ilerleme yeteneğinde olan en önemli nörodejeneratif hastalıklardır. Nörodejeneratif hastalıkların kesin bir tedavisi henüz bulunmamakla birlikte; hastalığın seyrini yavaşlatarak insanların yaşam kalitelerini artırmayı hedefleyen tedavi yaklaşımları uygulanmaktadır. Mevcut terapötik müdahaleler ve bu doğrultuda kullanılan ilaçların, kronik kullanımda ciddi yan etkiler meydana getirmiş olması, uygulanan tedavi stratejilerinde karşılaşılan en önemli güçlükler arasında olup; bu durum hastaların geleneksel tıp uygulamalarına yönelmesine neden olmuştur. Bu bağlamda, nörodejenerasyonda beyin hasarlarının iyileşmesine katkıda bulunan ve yeni sinaps oluşumlarını teşvik ederek öğrenme ve hafıza fonksiyonlarını artırıcı yönde potansiyele sahip olan nöroprotektif özellikteki tıbbi bitkilerle yapılan tamamlayıcı tıp uygulamaları günümüzde önemli bir yaklaşım haline gelmiştir. Tıbbi bitkiler; ihtiva ettikleri fitokimyasallar sayesinde, nörodejeneratif hastalık gelişimi ile ilişkili hücresel ve moleküler mekanizmalarda etkili olarak, hastalığın prognozunu yavaşlatmaya ciddi anlamda katkı sağlamaktadır. Bu derlemede, nörodejeneratif hastalıkların mekanizmaları ve bu hastalıkların tedavisinde terapötik ajan olarak kullanılma potansiyeline sahip olan nöroprotektif tıbbi bitkiler ve fitokimyasallar kaleme alınmıştır.

Anahtar Kelimeler

• nörodejeneratif bozukluklar
• tıbbi bitkiler
• tamamlayıcı tıp
• nöroprotektif
• geleneksel tıp

Medicinal Plants and Phytochemicals as Neuroprotective Agents in the Treatment of Neurodegenerative Diseases

Öz

Neurodegenerative diseases are multifactorial diseases characterized by structural and functional degeneration and/or death of nerve cells. Alzheimer's, Parkinson's, Huntington's, Amyotrophic Lateral Sclerosis and Multiple Sclerosis are the most important neurodegenerative diseases that negatively affect people's quality of life and can progress rapidly. Although there has been no definitive treatment for neurodegenerative diseases, yet; treatment approaches aiming to increase the people's quality of life by slowing the course of the disease are applied. The existing therapeutic interventions and the drugs used in this direction, causing serious side effects in chronic use, are among the most important difficulties encountered in the applied treatment strategies; which has caused patients to turn to traditional medicine practices. In this context, complementary medicine applications with neuroprotective medicinal plants, which contribute to the recovery of brain damage in neurodegeneration and have the potential to increase learning and memory functions by promoting the formation of new synapses, have become an important approach today. Thanks to the phytochemicals, medicinal plants contribute significantly to reduce the prognosis of the disease by effective in the cellular and molecular mechanisms associated with the development of neurodegenerative disease. The mechanisms of neurodegenerative diseases and neuroprotective medicinal plants and phytochemicals that have the potential to be used as therapeutic agents in the treatment of these diseases are summarized in this review.

Anahtar Kelimeler

• neurodegenerative disorders
• medicinal plants
• complementary medicine
• neuroprotective
• traditional medicine

Kaynakça

1. [1] Gezici, S., & Şekeroğlu, N. (2019a). Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anti-Cancer Agents in Medicinal Chemistry, 19(1), 101-111.
2. [2] Baydar, H. (2020) Tıbbi ve aromatik bitkiler bilimi ve teknolojisi. (8.baskı). Ankara: Nobel Akademik Yayınları.
3. [3] Şenkal, B. C. (2020). The role of secondary metabolites obtained from medicinal and aromatic plants in our lives. ISPEC Journal of Agricultural Sciences, 4(4), 1071-1079.
4. [4] Sam, S. (2019). Importance and effectiveness of herbal medicines. Journal of Pharmacognosy and Phytochemistry, 8(2), 354-357.
5. [5] Bozyel, M. E., Bozyel, E. M., Canlı, K., & Altuner, E. M. (2019). Anticancer uses of medicinal plants in Turkish traditional medicine. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, 22, 465-484.
6. [6] Tesfahuneygn, G., & Gebreegziabher, G. (2019). Medicinal plants used in traditional medicine by ethiopians: A review article. J Respir Med Lung Dis, 4(1), 1-3.
7. [7] Ramakrishna, W., Kumari, A., Rahman, N., & Mandave, P. Anticancer activities of plant secondary metabolites: Rice callus suspension culture as a new paradigm. Rice Science, 28(1), 13-30.
8. [8] Gezici, S., & Sekeroglu, N. (2019b). Neuroprotective potential and phytochemical composition of acorn fruits. Industrial Crops and Products, 128, 13-17.

9. [9] Ahmad, A., Patel, V., Xiao, J., & Khan, M. M. (2020). The role of neurovascular system in neurodegenerative diseases. Molecular Neurobiology, 57(11), 4373-4393.
10. [10] Scheiblich, H., Trombly, M., Ramirez, A., & Heneka, M. T. (2020). Neuroimmune connections in aging and neurodegenerative diseases. Trends in immunology, 41(4), 300-312.
11. [11] Teixeira, M. I., Lopes, C. M., Amaral, M. H., & Costa, P. C. (2020). Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseases. European Journal of Pharmaceutics and Biopharmaceutics, 149, 192-217.
12. [12] Cassano, T., Villani, R., Pace, L., Carbone, A., Bukke, V. N., Orkisz, S., ... & Serviddio, G. (2020). From Cannabis sativa to cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Frontiers in pharmacology, 11.
13. [13] Luthra, R., & Roy, A. (2021). Role of medicinal plants against neurodegenerative diseases. Current Pharmaceutical Biotechnology. McKinnon, P. J. (2013). Maintaining genome stability in the nervous system. Nature neuroscience, 16(11), 1523.
14. [14] Senol, F. S., Sekeroglu, N., Gezici, S., Kilic, E., & Orhan, İ. E. (2018). Neuroprotective potential of the fruit (acorn) from Quercus coccifera L. Turkish Journal of Agriculture and Forestry, 42(2), 82-87.
15. [15] Ratheesh, G., Tian, L., Venugopal, J. R., Ezhilarasu, H., Sadiq, A., Fan, T. P., & Ramakrishna, S. (2017). Role of medicinal plants in neurodegenerative diseases. Biomanufacturing Reviews, 2(1), 1-16
16. [16] Lalotra, S., & Vaghela, J. S. (2019). Scientific reports of medicinal plants used for the prevention and treatment of neurodegenerative diseases. Pharmaceutical and Biosciences Journal, 15-25.
17. [17] Rekatsina, M., Paladini, A., Piroli, A., Zis, P., Pergolizzi, J. V., & Varrassi, G. (2020). Pathophysiology and therapeutic perspectives of oxidative stress and neurodegenerative diseases: a narrative review. Advances in therapy, 37(1), 113-139.
18. [18] Guerreiro, S., Privat, A. L., Bressac, L., & Toulorge, D. (2020). CD38 in Neurodegeneration and Neuroinflammation. Cells, 9(2), 471.
19. [19] Ha, Z. Y., Mathew, S., & Yeong, K. Y. (2020). Butyrylcholinesterase: a multifaceted pharmacological target and tool. Current Protein and Peptide Science, 21(1), 99-109.
20. [20] Wyss-Coray, T. (2016). Ageing, neurodegeneration and brain rejuvenation. Nature, 539(7628), 180-186.
21. [21] Jeppesen, D. K., Bohr, V. A., & Stevnsner, T. (2011). DNA repair deficiency in neurodegeneration. Progress in neurobiology, 94(2), 166-200.
22. [22] McKinnon, P. J. (2013). Maintaining genome stability in the nervous system. Nature neuroscience, 16(11), 1523.
23. [23] Walker, L. C., & LeVine, H. (2000). The cerebral proteopathies. Molecular neurobiology, 21(1), 83-95.
24. [24] Luheshi, L. M., Crowther, D. C., & Dobson, C. M. (2008). Protein misfolding and disease: from the test tube to the organism. Current opinion in chemical biology, 12(1), 25-31.
25. [25] Jasiecki, J., & Wasąg, B. (2019). Butyrylcholinesterase protein ends in the pathogenesis of Alzheimer’s disease could BCHE genotyping be helpful in Alzheimer’s therapy. Biomolecules, 9(10), 592.
26. [26] Dobson, C. M. (2003). Protein folding and misfolding. Nature, 426(6968), 884-890.
27. [27] Rubinsztein, D. C. (2006). The roles of intracellular protein-degradation pathways in neurodegeneration. Nature, 443(7113), 780-786.
28. [28] Kim, Y. J., & Uyama, H. (2005). Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cellular and molecular life sciences CMLS, 62(15), 1707-1723.
29. [29] Scheff, S. W., & Price, D. A. (2006). Alzheimer's disease-related alterations in synaptic density: neocortex and hippocampus. Journal of Alzheimer's Disease, 9(s3), 101-115.
30. [30] Tao, Z., Dong, B., Teng, Z., & Zhao, Y. (2020). The classification of enzymes by deep learning. IEEE Access, 8, 89802-89811.
31. [31] Vandenberghe, L., Karp, S. G., Binder Pagnoncelli, M. G., von Linsingen Tavares, M., Libardi Junior, N., Valladares Diestra, K., Viesser, J. A., & Soccol, C. R. (2020). Classification of enzymes and catalytic properties. In Biomass, Biofuels, Biochemicals (pp. 11–30). Elsevier.
32. [32] Bora, N. (2019).‘’Aristolochia bodamae Dingler (Aristolochiaceae) Kök Ekstraktlarının in vitro Antioksidan, Antibakteriyel ve Enzim İnhibisyon Aktivitelerinin Araştırılması’’, Yüksek Lisans Tezi, Ondokuz Mayıs Üniversitesi, Fen Bilimleri Enstitüsü, Samsun.
33. [33] Pohanka, M. (2012). Acetylcholinesterase inhibitors: a patent review (2008–present). Expert opinion on therapeutic patents, 22(8), 871-886.
34. [34] Xing, S., Li, Q., Xiong, B., Chen, Y., Feng, F., Liu, W., & Sun, H. (2020). Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism. Medicinal Research Reviews.
35. [35] Nagatsu, T., Nakashima, A., Ichinose, H., & Kobayashi, K. (2019). Human tyrosine hydroxylase in Parkinson’s disease and in related disorders. Journal of Neural Transmission, 126(4), 397-409.
36. [36] Çelikler, Ö. (2017). ‘’Bitkisel Kaynaklı Yeni Tirozinaz İnhibitörlerinin Belirlenmesi Üzerinde Farmakognozik Araştırmalar ‘’, Doktora Tezi, Gazi Üniversitesi, Sağlık Bilimleri Enstitüsü, Ankara.
37. [37] Copeland, R. A., Harpel, M. R., & Tummino, P. J. (2007). Targeting enzyme inhibitors in drug discovery. Expert opinion on therapeutic targets, 11(7), 967-978.
38. [38] Smith, J. H., & Simons, C. (2004). Development of enzyme inhibitors as drugs. Enzymes and their inhibitors drug development, 190-328.
39. [39] Lermi, M. (2018). ‘’Isatis cappadocica’ nın Antioksidan, Antimikrobiyal, Tirozinaz İnhibitör ve Sitotoksik Etkilerinin İncelenmesi’’, Yüksek Lisans Tezi, Karadeniz Teknik Üniversitesi, Sağlık Bilimleri Enstitüsü, Trabzon.
40. [40] Zilbeyaz, K., Stellenboom, N., Guney, M., Oztekin, A., & Senturk, M. (2018). Effects of aryl methanesulfonate derivatives on acetylcholinesterase and butyrylcholinesterase. Journal of biochemical and molecular toxicology, 32(11), e22210.
41. [41] Türkan, F., & Atalar, M. N. The toxicological impact of some agents on glutathione S-transferase and cholinesterase enzymes. In Toxicology (pp. 281-290). Academic Press.
42. [42] Zhang, P., Fu, C., Xiao, Y., Zhang, Q., & Ding, C. (2020). Copper (II) complex as a turn on fluorescent sensing platform for acetylcholinesterase activity with high sensitivity. Talanta, 208, 120406.
43. [43] Chrouda, A., Zinoubi, K., Soltane, R., Alzahrani, N., Osman, G., Al-Ghamdi, Y. O., ... & Jaffrezic Renault, N. (2020). An acetylcholinesterase inhibition-based biosensor for aflatoxin B1 detection using sodium alginate as an immobilization matrix. Toxins, 12(3), 173.
44. [44] Koç, F. (2019). ‘Rutinhidrat’ın Antioksidan Kapasitesinin Belirlenmesi ve İnsan Karbonik Anhidraz, Asetilkolinesteraz, Bütirilkolinesteraz Enzimleri Üzerine Etkisinin İncelenmesi’, Yüksek Lisans Tezi, Atatürk Üniversitesi, Fen Bilimleri Enstitüsü, Erzurum.
45. [45] Dias, C., & Rauter, A. P. (2015). Carbohydrates and Glycomimetics in Alzheimer's Disease therapeutics and Diagnosis. in Carbohydrates in Drug Design and Discovery (pp. 180-208). Royal Society of Chemistry.
46. [46] Tekin, Z. (2018). ‘’Türkiye İçin Endemik Bir Tür Olan Nepeta congesta var. congesta’nın (Lamiaceae) Antioksidan Özelliklerinin ve Enzim İnhibitör Etkisinin Değerlendirilmesi’’, Yüksek Lisans Tezi, Necmettin Erbakan Üniversitesi, Fen Bilimleri Enstitüsü, Konya.
47. [47] Joubert, J., & Kapp, E. (2020). Discovery of 9-phenylacridinediones as highly selective butyrylcholinesterase inhibitors through structure-based virtual screening. Bioorganic & medicinal chemistry letters, 30(9), 127075.
48. [48] Mendes, E., Perry, M. D. J., & Francisco, A. P. (2014). Design and discovery of mushroom tyrosinase inhibitors and their therapeutic applications. Expert opinion on drug discovery, 9(5), 533-554.
49. [49] Gillbro, J. M., & Olsson, M. J. (2011). The melanogenesis and mechanisms of skin‐lightening agents–existing and new approaches. International Journal of cosmetic science, 33(3), 210-221.
50. [50] Agarwal, P., Singh, M., Singh, J., & Singh, R. P. (2019). Microbial Tyrosinases: A Novel Enzyme, Structural Features, and Applications. In Applied Microbiology and Bioengineering (pp. 3-19). Academic Press.
51. [51] Gasser, T. (2001). Genetics of Parkinson's disease. Journal of neurology, 248(10), 833-840.
52. [52] Tocco, G., Fais, A., Meli, G., Begala, M., Podda, G., Fadda, M. B., ... & Berretta, S. (2009). PEG-immobilization of cardol and soluble polymer-supported synthesis of some cardol–coumarin derivatives: Preliminary evaluation of their inhibitory activity on mushroom tyrosinase. Bioorganic & medicinal chemistry letters, 19(1), 36-39.
53. [53] Singhal, A. K., Naithani, V., & Bangar, O. P. (2012). Medicinal plants with a potential to treat Alzheimer and associated symptoms. International Journal of Nutrition, Pharmacology, Neurological Diseases, 2(2), 84.
54. [54] Munawar, T., Bibi, Y., & Ahmad, F. (2020). Ethnomedicinal Study of Plants used for Neurodegenerative Diseases: A Review: Ethnomedicinal study of plants used for Neurodegenerative Diseases. Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, 57(3), 13-26.
55. [55] Rojas, P., Serrano-García, N., Medina-Campos, O. N., Pedraza-Chaverri, J., Maldonado, P. D., & Ruiz-Sánchez, E. (2011). S-Allylcysteine, a garlic compound, protects against oxidative stress in 1-methyl-4-phenylpyridinium-induced parkinsonism in mice. The Journal of nutritional biochemistry, 22(10), 937-944.
56. [56] Sigurdsson, S., & Gudbjarnason, S. (2007). Inhibition of acetylcholinesterase by extracts and constituents from Angelica archangelica and Geranium sylvaticum. Zeitschrift für Naturforschung C, 62(9-10), 689-693.
57. [57] Wszelaki, N., Paradowska, K., Jamróz, M. K., Granica, S., & Kiss, A. K. (2011). Bioactivity-guided fractionation for the butyrylcholinesterase inhibitory activity of furanocoumarins from Angelica archangelica L. roots and fruits. Journal of agricultural and food chemistry, 59(17), 9186-9193.
58. [58] Gupta, A., Singh, R., & Kakar, S. (2019). Alzheimer’s Disease Treatment with Herbal Prospective. International Journal of Health and Biological Sciences, 2(4), 13-18.
59. [59] Malar, D. S., Prasanth, M. I., Brimson, J. M., Sharika, R., Sivamaruthi, B. S., Chaiyasut, C., & Tencomnao, T. (2020). Neuroprotective properties of green tea (Camellia sinensis) in Parkinson’s disease: A review. Molecules, 25(17), 3926
60. [60] Perry, E., & Howes, M. J. R. (2011). Medicinal plants and dementia therapy: herbal hopes for brain aging?. CNS neuroscience & therapeutics, 17(6), 683-698.
61. [61] Currais, A., Quehenberger, O., Armando, A. M., Daugherty, D., Maher, P., & Schubert, D. (2016). Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. NPJ aging and mechanisms of disease, 2(1), 1-8.
62. [62] Cassano, T., Villani, R., Pace, L., Carbone, A., Bukke, V. N., Orkisz, S., ... & Serviddio, G. (2020). From Cannabis sativa to cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Frontiers in pharmacology, 11, 124.
63. [63] Jung, H. A., Ali, M. Y., Jung, H. J., Jeong, H. O., Chung, H. Y., & Choi, J. S. (2016). Inhibitory activities of major anthraquinones and other constituents from Cassia obtusifolia against β-secretase and cholinesterases. Journal of ethnopharmacology, 191, 152-160.
64. [64] Turkiewicz, I. P., Wojdyło, A., Tkacz, K., Nowicka, P., Golis, T., & Bąbelewski, P. (2020). ABTS On-line antioxidant, α-amylase, α-glucosidase, pancreatic lipase, acetyl-and butyrylcholinesterase inhibition activity of Chaenomeles fruits determined by polyphenols and other chemical compounds. Antioxidants, 9(1), 60.
65. [65] Chen, J. F., Steyn, S., Staal, R., Petzer, J. P., Xu, K., Van der Schyf, C. J., ... & Schwarzschild, M. A. (2002). 8-(3-Chlorostyryl) caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A2A receptor antagonism. Journal of Biological Chemistry, 277(39), 36040-36044.
66. [66] Gönder, M., & Sanlıer, N. (2014). Kahve Tüketimi ve Nörodejeneratif Hastalıklarla Iliskisi. Turkiye Klinikleri Journal of Neurology, 9(2), 67-72.
67. [67] Mahomoodally, M. F., Dursun, P. D., & Venugopala, K. N. (2021). Collinsonia canadensis L. In Naturally Occurring Chemicals Against Alzheimer's Disease (pp. 373-377). Academic Press.
68. [68] Balkrishna, A., Thakur, P., & Varshney, A. (2020). Phytochemical profile, pharmacological attributes and medicinal properties of convolvulus prostratus–A cognitive enhancer herb for the management of neurodegenerative etiologies. Frontiers in pharmacology, 11, 171.
69. [69] Finley, J. W., & Gao, S. (2017). A perspective on Crocus sativus L.(Saffron) constituent crocin: a potent water-soluble antioxidant and potential therapy for Alzheimer’s disease. Journal of agricultural and food chemistry, 65(5), 1005-1020.
70. [70] Ojha, R. P., Rastogi, M., Devi, B. P., Agrawal, A., & Dubey, G. P. (2012). Neuroprotective effect of curcuminoids against inflammation-mediated dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Journal of Neuroimmune Pharmacology, 7(3), 609-618.
71. [71] Yuliani, S., Mustofa, & Partadiredja, G. (2019). The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats. Nutritional neuroscience, 22(11), 797-804.
72. [72] Rashed, A., Abd Rahman, A. Z., & Rathi, D. N. G. (2021). Essential oils as a potential Neuroprotective remedy for age-related neurodegenerative diseases: A review. Molecules, 26(4), 1107.
73. [73] Klemow, K. M., Bartlow, A., Crawford, J., Kocher, N., Shah, J., & Ritsick, M. (2011). Medical attributes of St. John’s wort (Hypericum perforatum). Herbal medicine: biomolecular and clinical aspects, 211-237.
74. [74] Guo, S. S., Gao, X. F., Gu, Y. R., Wan, Z. X., Lu, A., Qin, Z. H., & Luo, L. (2016). Preservation of cognitive function by Lepidium meyenii (maca) is associated with improvement of mitochondrial activity and upregulation of autophagy-related proteins in middle-aged mouse cortex. Evidence-based complementary and alternative medicine, 2016.
75. [75] Chang, R. C. C., & So, K. F. (2008). Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far?. Cellular and Molecular Neurobiology, 28(5), 643-652.
76. [76] Chandrashekhar, V. M., Ranpariya, V. L., Ganapaty, S., Parashar, A., & Muchandi, A. A. (2010). Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats. Journal of ethnopharmacology, 127(3), 645-651.
77. [77] Kuk, E. B., Jo, A. R., Oh, S. I., Sohn, H. S., Seong, S. H., Roy, A., ... & Jung, H. A. (2017). Anti-Alzheimer’s disease activity of compounds from the root bark of Morus alba L. Archives of pharmacal research, 40(3), 338-349.
78. [78] Javidi, S., Razavi, B. M., & Hosseinzadeh, H. (2016). A review of neuropharmacology effects of Nigella sativa and its main component, thymoquinone. Phytotherapy research, 30(8), 1219-1229.
79. [79] Prinsloo, D., Van Dyk, S., Petzer, A., & Petzer, J. P. (2019). Monoamine oxidase inhibition by kavalactones from kava (piper methysticum). Planta medica, 85(14/15), 1136-1142.
80. [80] Jang, J. Y., Kim, H. N., Kim, Y. R., Choi, Y. W., Choi, Y. H., Lee, J. H., ... & Choi, B. T. (2013). Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis in primary cultured cortical neurons. Journal of Ethnopharmacology, 145(1), 261-268.
81. [81] Lin, C. M., Lin, R. D., Chen, S. T., Lin, Y. P., Chiu, W. T., Lin, J. W., ... & Lee, M. H. (2010). Neurocytoprotective effects of the bioactive constituents of Pueraria thomsonii in 6-hydroxydopamine (6-OHDA)-treated nerve growth factor (NGF)-differentiated PC12 cells. Phytochemistry, 71(17-18), 2147-2156.
82. [82] Park, S. E., Kim, S., Sapkota, K., & Kim, S. J. (2010). Neuroprotective effect of Rosmarinus officinalis extract on human dopaminergic cell line, SH-SY5Y. Cellular and molecular neurobiology, 30(5), 759-767
83. [83] Alvi, S. S., Ahmad, P., Ishrat, M., Iqbal, D., & Khan, M. S. (2019). Secondary metabolites from rosemary (Rosmarinus officinalis L.): Structure, biochemistry and therapeutic implications against neurodegenerative diseases. In Natural Bio-active Compounds (pp. 1-24). Springer, Singapore.
84. [84] Sancheti, S., Um, B. H., & Seo, S. Y. (2010). 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose: A cholinesterase inhibitor from Terminalia chebula. South African Journal of Botany, 76(2), 285-288.
85. [85] Li, J., & Hao, J. (2019). Treatment of neurodegenerative diseases with bioactive components of Tripterygium wilfordii. The American journal of Chinese medicine, 47(04), 769-785.
86. [86] Liu, Y., Chen, H. L., & Yang, G. (2010). Extract of Tripterygium wilfordii Hook F protect dopaminergic neurons against lipopolysaccharide-induced inflammatory damage. The American journal of Chinese medicine, 38(04), 801-814.
87. [87] Shin, S. J., Jeong, Y., Jeon, S. G., Kim, S., Lee, S. K., Choi, H. S., & Moon, M. (2018). Uncaria rhynchophylla ameliorates amyloid beta deposition and amyloid beta-mediated pathology in 5XFAD mice. Neurochemistry international, 121, 114-124.
88. [88] Rapaka, D., Bitra, V. R., Vishala, T. C., & Akula, A. (2019). Vitis vinifera acts as anti-Alzheimer's agent by modulating biochemical parameters implicated in cognition and memory. Journal of Ayurveda and integrative medicine, 10(4), 241-247.
89. [89] Fouad, G. I., & Rizk, M. Z. (2019). Possible neuromodulating role of different grape (Vitis vinifera L.) derived polyphenols against Alzheimer’s dementia: treatment and mechanisms. Bulletin of the National Research Centre, 43(1), 1-13.
90. [90] Dar, N. J. (2020). Neurodegenerative diseases and Withania somnifera (L.): An update. Journal of ethnopharmacology, 256, 112769.
91. [91] Talebi, M., Ilgün, S., Ebrahimi, V., Talebi, M., Farkhondeh, T., Ebrahimi, H., & Samarghandian, S. (2021). Zingiber officinale ameliorates Alzheimer’s disease and cognitive impairments: lessons from preclinical studies. Biomedicine & Pharmacotherapy, 133, 111088.