Treatment of Alzheimer’s Disease by Natural Products

Abstract

Alzheimer’s disease is a neurological disorder that progressively affects the brain cells. It is sometimes accompanied with dementia and commonly seen in elderly people. It ultimately leads to impaired cognitive functions and loss of memory. Widely used drugs such as donepezil and galantamine successfully abate mild to moderate symptoms of the disease though they have profound side effects. Natural products have been a source of medicine for over thousands of years. Plant secondary metabolites such as alkaloids, flavonoids, terpenoids, etc. are major sources of such medicines. In recent times, the use of natural products to treat various diseases has gained a lot of popularity. Extensive research is being undertaken to identify and isolate various natural products that can be used to not only reduce the disease symptoms but also as a permanent cure. The review article aims to summarize the effects of various natural products and their neuroprotective mechanisms that can be helpful to cure Alzheimer’s disease.

Keywords

• Acetylcholine esterase (AChE)
• Alzheimer’s disease (AD)
• plant secondary metabolites
• Aβ aggregation

References

1. 1. Akhondzadeh, S., Sabet, M.S., Harirchian, M.H., Togha, M., Cheraghmakani, H., Razeghi, S., Hejazi, S.S., Yousefi, M.H., Alimardani, R., Jamshidi, A., Zare, F., Moradi, A., 2010. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16‐week, randomized and placebo‐controlled trial. J. Clin. Pharm. Ther. 35, 581-588.
2. 2. Abd-Razak, S.I., Hamzah, M.S.A., Yee, F.C., Kadir, M.R.A., Nayan, N.H.M., 2017. A review on medicinal properties of Saffron toward major diseases. J. Herbs Spices Med. Plants. 23, 98-116.
3. 3. Ahmed, T., Javed, S., Javed, S., Tariq, A., Samec, D., Tejada, S., Nabavi, S.F., Braidy, N., Nabavi, S.M., 2017. Resveratrol and Alzheimer’s disease: mechanistic insights. Mol. Neurobiol. 54, 2622-2635.
4. 4. Ali, A. 2020. Herbs that heal: the philanthropic behavior of nature. Ann. Phytomed. 9(1), 7-17.
5. 5. Ali, F., Rahul, Jyoti, S., Naz, F., Ashafaq, M., Shahid, M, Siddique, Y.H., 2019. Therapeutic potential of luteolin in transgenic Drosophila model of Alzheimer’s disease. Neurosci. Lett. 692, 90-99.
6. 6. Ansari, N., Khodagholi, F., 2013. Natural products as promising drug candidates for the treatment of Alzheimer’s disease: molecular mechanism aspect. Curr. Neuropharmacol. 11, 414-423.
7. 7. Arbo, B.D., André-Miral, C., Nasre-Nasser, R.G., Schimith, L.E., Santos, M.G., Costa-Silva, D., Muccillo-Baisch, A.L., Hort, M.A., 2020. Resveratrol derivatives as potential treatments for Alzheimer’s and Parkinson’s disease. Front. Aging Neurosci. 12, 103.
8. 8. Aziz, N., Kim, M.Y., Cho, J.Y., 2018. Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies. J. Ethanopharmacol. 225, 342-358.

9. 9. Bahar, E., Kim, J.Y., Yoon, H., 2017. Quercetin attenuates manganese induced neuroinflammation by alleviating oxidative stress through regulation of apoptosis, iNOS/NF-kB and HO-1/Nrf2 pathways. Int. J. Mol. Sci. 18, 1989.
10. 10. Bhat, A., Mahalakshmi, A.M., Ray, B., Tuladhar, S., Hediyal, T.A., Manthiannem, E., Padamati, J., Chandra, R., Chidambaram, S.B., Sakharkar, M.K., 2019. Benefits of curcumin in brain disorders. BioFactors. 1-24.
11. 11. Bui, T.T., Nguyen, T.H., 2017. Natural product for the treatment of Alzheimer’s disease. J. Basic Clin. Physiol. Pharmacol. 28, 413-423.
12. 12. Calfio, C., Gonzalez, A., Singh, S.K., Rojo, L.E, Maccioni, R.B., 2020. The emerging role of nutraceuticals and phytochemicals in the prevention and treatment of Alzheimer’s disease. J. Alzheimers Dis. 77, 33-51.
13. 13. Chen, C.L., Tsai, W.H., Chen, C.J., Pan, T.M., 2015. Centella asiatica extract protects against amyloid β1-40 -induced neurotoxicity in neuronal cells by activating the antioxidative defence system. J. Trad. Complement. Med. 6, 362-369.
14. 14. Choi, J.G., Kim, S.Y, Jeoung, M., Oh, M.S., 2018. Pharmacotherapeutic potential of ginger and its compounds in age-related neurological disorders. Pharmacol. Ther. 182, 56-69.
15. 15. Chou, C.P., Wang, Y.C., Chang, S.J., Liu, P.H., Kuo, S.M., 2012. Evaluation of the effects of chitosan hemostasis dressings on hemorrhage caused by breast biopsy. Breast Care (Basel). 7, 220-224.
16. 16. D’Onfrio, G., Sancarlo, D., Ruan, Q., Yu, Z., Panza, F., Daniele, A., Greco, A., Seripa, D., 2017. Phytochemicals in the treatment of Alzheimer’s disease: a systematic review. Curr. Drug Targets. 18, 1487-1498.
17. 17. Dar, R.A., Shahnawaz, M., Rasool, S., Qazi, P.H., 2017. Natural product medicines: a literature update. J. Phytopharmacol. 6, 340-342.
18. 18. Darakhshan, S., Pour, A.B., Colagar, A.H., Sisakhtnezhad., S., 2015. Thymoquinone and its therapeutic potentials. Pharmacol. Res. 96, 138-158.
19. 19. Deshpande, P., Gogia, N., Singh, A., 2019. Exploring the efficacy of natural products in alleviating Alzheimer’s disease. Neural Regen. Res. 14, 1321-1329.
20. 20. Dey, A., Bhattacharya, R., Mukherjee, A., Pandey, D.K., 2017. Natural products against Alzheimer's disease: pharmacotherapeutics and biotechnological interventions. Biotechnol. Adv. 35, 178-216.
21. 21. Dubey, T., Chinnathambi, S., 2019. Brahmi (Bacopa monnieri): An ayurvedic herb against the Alzheimer's disease. Arch. Biochem. Biophys. 676, 108153.
22. 22. Fachel, F.N.S., Schuh, R.S., Veras, K.S., Bassani, V.L., Koester, L.S., Henriques, A.T., Braganhol, E., Teixeira, H.F., 2019. An overview of the neuroprotective potential of rosmarinic acid and its association with nanotechnology-based delivery systems: a novel approach to treating neurodegenerative disorders. Neurochem. Int. 122, 47-58.
23. 23. Farooqui, A., Farooqui, T., 2017. Garlic and its effects in neurological disorders. In Neuroprotective Effects of Phytochemicals in Neurological Disorders, First eds. John Wiley & Sons, Inc., pp. 113-131.
24. 24. Grzanna, R., Phan, P., Polotsky, A., Lindmark, L., Frondoza, C.G., 2004. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes. J. Altern. Complement. Med. 10, 1009-1013.
25. 25. Gao, J., Inagaki, Y., Li, X., Kokudo, N., Tang, W., 2013. Research progress on natural products from traditional Chinese medicine in treatment of Alzheimer's disease. Drug Discov. Ther. 7, 46-57.
26. 26. Habtemariam, S., 2018. Molecular pharmacology of rosmarinic and salvianolic acids: potential seeds for Alzheimer’s and Vascular Dementia drugs. Int. J. Mol. Sci. 19, 458.
27. 27. Hao, C., Wang, W., Wang, S., Zhang, L., Guo, Y., 2017. An overview of the protective effects of chitosan and acetylated chitosan oligosaccharides against neuronal disorders. Mar. Drugs. 15, 89.
28. 28. Hussain, A., Tabrez, E.S., Mavrych, V., Bolgova, O., Peela, J.R., 2018. Caffeine: a potential protective agent against cognitive decline in Alzheimer’s disease. Crit. Rev. Eukaryot. Gene Expr. 28, 67-72.
29. 29. Ijaz, H., Tulain, U.R., Qureshi, J., Danish, Z., Musayab, S., Akhtar, M.F., Saleem, A., Khan, K.K., Zaman, M., Waheed, I., Khan, I., Abdel-Daim, M., 2017. Nigella sativa (prophetic medicine): a review. Pak. J. Pharm. Sci. 30, 229-234.
30. 30. Iranshahy, M., Javadi, B., 2019. Diet therapy for the treatment of Alzheimer’s disease in view of traditional Persian medicine: a review. Iran. J. Basic Med. Sci. 22, 1102-1117.
31. 31. Jabir, N.R., Khan, F.R., Tabrez, S., 2018. Cholinesterase targeting by polyphenols: a therapeutic approach for the treatment of Alzheimer's disease. CNS Neurosci. Ther. 24, 753-762.
32. 32. Kaur, N., Sarkar, B., Gill, I., Kaur, S., Mittal, S., Dhiman, M., Padal, P.R., Perez-Polo, R., Mantha, A.K., 2017. Indian herbs and their therapeutical potential against Alzheimer’s disease and other neurological disorders. In Neuroprotective Effects of Phytochemicals in Neurological Disorders, First eds. John Wiley & Sons, Inc., pp. 79-112.
33. 33. Khatri, S., Paramanya, A., Ali., A. 2018 Phenolic acids and their health promoting activity. In Plant and Human Health, Volume 2 - Phytochemistry and Molecular Aspects, Munir Ozturk and Khalid Rehman Hakeem (Eds.). Springer, Switzerland. Pp. 661-680
34. 34. Khodagholi, F., Eftekharzadeh, B., Maghsoudi, N., Rezaei, P.F., 2010. Chitosan prevents oxidative stress-induced amyloid beta formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-kappaB. Mol. Cell. Biochem. 337, 39-51.
35. 35. Kumar A, Sharma S., 2020. Donepezil. In: StatPearls [Internet]. Treasure Island (FL), StatPearls Publishing LLC.
36. 36. Kwon, Y., 2017. Luteolin as a potential preventive and therapeutic candidate for Alzheimer's disease. Exp. Gerontol. 95, 39-43.
37. 37. Leone, S., Recinella, L., Chiavaroli, A., Orlando, G., Ferrante, C., Leporini, L., Brunetti, L., Menghini, L., 2017. Phytotherapic use of Crocus sativus L. (Saffron) and its potential applications: a brief review. Phytother. Res. 32, 2364-2375.
38. 38. Maleki, S.N., Aboutaleb, N., Souri, F., 2018. Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines. J. Chem. Neuroanat. 87, 54-59.
39. 39. Manap, A.S.A., Vidyabalan, S., Madhavan, P., Chia, Y.Y., Arya, A., Wong, E.H., Rizwan, F., Bindal, U., Koshy, S., 2019. Bacopa monnieri, a neuroprotective lead in Alzheimer disease: a review on its properties, mechanisms of action, and preclinical and clinical studies. Drug Target Insights. 13, 1-13.
40. 40. Memariani, Z., Farzaei, M. H., Ali, A., Momtaz, S. 2020. Nutritional and bioactive characterization of unexplored food rich in phytonutrients. In Phytonutrients in Food. S. M. Nabavi, I. Suntar, D. Barreca, H. Khan, eds. Woodhead Publishing, pp. 157-175)
41. 41. Mirmosayyeb, O., Tanhaeu, A., Sohrabi, H.R., Martins, R.N., Tanhaei, M., Najafi, M.A., Safaei, A., Meamar, R., 2017. Possible role of common spices as a preventive and therapeutic agent for Alzheimer’s disease. Int. J. Prev. Med. 8, 5.
42. 42. Sahardi, N.F.N.M., Makpol, S., 2019. Ginger (Zingiber officinale Roscoe) in the prevention of ageing and degenerative diseases: review of current evidence. Evid. Based Complement. Alternat. Med. 2019, 5054395.
43. 43. Nabavi, S.F., Khan, H., D’Onofrio, G., Šamec, D., Shirooie, S., Dehpor, A.R., Argüelles, S., Sabtemariam, S., Sobarzo-Sanchez, E., 2017. Apigenin as neuroprotective agent: of mice and men. Pharmacol. Res. 128, 359-365.
44. 44. Nemetchek, M.D., Stierle, A.A., Stierle, D.B., Lurie, D.I., 2016. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. J. Ethnopharmacol. 197, 92-100.
45. 45. Ng, Y.P., Or, T.C.T., Ip, N.Y., 2015. Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem. Int. 89, 260-270.
46. 46. Ouyang, Q.Q., Zhao, S., Li, S.D., Song, C., 2017. Application of chitosan, chitooligosaccharide, and their derivatives in the treatment of Alzheimer’s disease. Mar. Drugs. 15, 322.
47. 47. Panche, A.N., Diwan, A.D., Chandra, S.R., 2016. Flavonoids: an overview. J. Nutr. Sci. 5, e47.
48. 48. Prakash, V., Jaiswal, N., Srivastava, M., 2017. A review on medicinal properties of Centella asiatica. Asian J. Pharm. Clin. Res. 10, 69-74.
49. 49. Rather, M.A., Thenmohzi, A.J., Manivasagam, T., Bharathi, M.D., Essa, M., Guillemin, G.J., 2018. Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Front. Biosci. 10, 262-275.
50. 50. Sanabrio-Castro, A., Alvarado-Echeverría, I., Monge-Bonilla, C., 2017. Molecular pathogenesis of Alzheimer’s disease: an update. Ann. Neurosci. 24, 46-54.
51. 51. Santamaría, T.Z., Gómez, P.Y., Galindo, I.F., González, M.G., Vázquez, A.O., López, M.L., 2018. Pharmacogenetic studies in Alzheimer disease. Neurología. 1-15.
52. 52. Sathya, S., Kasi, P.D., 2018. The use of polyphenols for the treatment of Alzheimer’s disease. In Role of the Mediterranean Diet in the Brain and Neurodegenerative Diseases, T. Farooqui and A. Farooqui, eds. Academic Press, pp. 239-252.
53. 53. Senol, F.S., Slusarczyk, S., Matkowski, A., Perez-Garrido, A., Giron-Rodriguez, F., Ceron-Carrasco, J.P., den-Haan, H., Pena-Garcia, J., Perez-Sanchez, H., Domaradzki, K., Orhan, I.E., 2017. Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L. Phytochemistry. 133, 33-44.
54. 54. Shal, B., Ding, W., Ali, H., Kim, Y.S., Khan, S., 2018. Anti-neuroinflammatory potential of natural products in attenuation of Alzheimer’s disease. Front. Pharmacol. 9, 548.
55. 55. Songjiang, Z., Lixiang, W., 2009. Amyloid-beta associated with chitosan nano-carrier has favorable immunogenicity and permeates the BBB. AAPS Pharm. Sci. Tech. 10, 900-905.
56. 56. Taguchi, R., Hatayama, K., Takahashi, T. Hayashi, T., Sato, Y., Sato, D., Ohta, K., Nakano, H., Seki, C., Endo, Y., Tokuraku, K., Uwai, K., 2017. Structure-activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties. Eur. J. Med. Chem. 138, 1066-1075.
57. 57. Tang, M., Taghiblou, C., 2017. The mechanisms of action of curcumin in Alzheimer’s disease. J. Alzheimers Dis. 58, 1003-1016.
58. 58. Tundis, R., Loizzo, M.R., Nabavi, S.M., Orhan, I.E., Skalicka-Wozniak, K., D’Onofrio, G., Aiello, F., 2018. Natural compounds and their derivatives as multifunctional agents for the treatment of Alzheimer disease. In Discovery and Development of Neuroprotective Agents from Natural Products: Natural Products Drug Discovery, G. Brahmachari, eds. Elsevier, pp. 63-102.
59. 59. Vazhayll, B.K., Sundaram, R.S., Annapadian, V.M., Abhirama, B.R., Sudha, M., Thiyagarajan, T., Kalapana, K.G., Pushpa, S., 2014. Natural products and its derived drugs for the treatment of neurodegenerative disorders: Alzheimer's disease- a review. Br. Biomed. Bull. 2, 359-370.
60. 60. Yuan, H., Ma, Q., Ye, L., Piao, G., 2016. The traditional medicine and modern medicine from natural products. Molecules. 21, 559.
61. 61. Zeng, G¬.F., Zhang, Z.Y., Lu, L., Xiao, D.Q., Zong, S.H., He, J.M., 2013. Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats. Rejuvenation Res. 16, 124-133.
62. 62. Zhao, L., Wang, J.L., Liu, R., Li, X.X., Li, J.F., Zhang, L., 2013. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model. Molecules. 18, 9949-9965.