Potential Malaysian Medicinal Plants for The Treatment of Alzheimer’s Disease

Kesevan Rajah Kumaran^b, Mohamad Anuar Ahad^a, Mira Syahfriena Amir Rawa^b, Habibah Wahab^b, Zurina Hassan^a*

Public interest statement: Plants are rich source of chemical diversity and provides the initiation platform for any drug discovery programme. Identifying the potential plants with anti-cholinesterase activity provides a platform to develop more effective drugs for treatment of AD.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease that leads to dementia. AD is characterized by progressive loss of structure and function of neurons that results in neuronal death over time. In the late stage, patients have difficulties to carry out their daily activity as they lose bodily function and needs assistance of a caretaker. The cause of AD is poorly understood and there is no treatment to reverse the progressive loss of neurons in patients until now. Progressive loss of cholinergic neurons and a consequent decline in levels of acetylcholine (ACh) in the brain are the cause of cognitive deterioration in patients suffering AD. Inhibition of cholinesterase (ChE) which are involved in breakdown of ACh into acetic acid and choline may prevent ACh level from decreasing. Currently available drugs that act against ChE are donepezil, rivastigmine and galantamine. These drugs provide symptomatic relief and delays the progress of AD. However, this drugs often produce side effects in consumers. Recently, plants have been given attention as a source of drug to treat neurodegenerative diseases due to its efficiency and less side effect properties. Hence, this review highlights previously and newly discovered potential plants with anti-cholinesterase activity to treat AD. 

Key words: Alzheimer's, neurodegenerative disease, acetylcholine, plants

References

Amir, F., Wong, K., Eldeen, I., Asmawi, M., & Osman, H. (2013). Evaluation of Biological Activities of Extracts and Chemical Constituents of Mimusops elengi. Tropical Journal of Pharmaceutical Research, 12(4). 591-596.
https://doi.org/10.4314/tjpr.v12i4.22

Athikomkulchai, S., Lipipun, V., Leelawittayanont, T., Khanboon, A., & Ruangrungsi, N. (2008). Anti-herpes Simplex Virus Activity of Syzygium jambos. Journal of Health Research, 2008(22), 49-51.

Avila-Pena, D., Pena, N., Quintero, L., & Suarez-Roca, H. (2007). Antinociceptive Activity of Syzygium jambos Leaves Extract on Rats. Journal of Ethnopharmacology, 112(2), 380-385.
https://doi.org/10.1016/j.jep.2007.03.027
PMid:17478066

Ballard, C.G. (2002). Advances in the treatment of Alzheimer's disease: Benefits of dual cholinesterase inhibition. European Neurology, 47, 67-70.
https://doi.org/10.1159/000047952
PMid:11803198

Barr, R. D., Koekebakker, M. & Lawson, A. A. (1988). Acetylcholinesterase in the Human Erythron. II. Biochemical assay, American Journal of Hematology, 28, 260.
https://doi.org/10.1002/ajh.2830280409
PMid:3166338

Bartus, R. T. (2000). On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis. Experimental Neurology, 163, 495-529.
https://doi.org/10.1006/exnr.2000.7397
PMid:10833325

Campos, M. R., Ruiz, J. R., Chel-Guerrero, L., & Ancona, D. B. (2015). Coccoloba uvifera (L.) (Polygonaceae) Fruit: Phytochemical Screening and Potential Antioxidant Activity. Journal of Chemistry, 2015, 1-9.
https://doi.org/10.1155/2015/534954

Chitra, V., Tamilanban, T., Manasa, K., & Chitra, K. (2016). Cognitive and Anti-oxidant Property of Mimusops elengi Linn. in the Experimental Model of Alzheimer's Disease in Rats. International Journal of PharmTech Research, 9(3), 311-319.

Colovic, M. B., Krstic, D. Z., Lazarevic-Pasti, T. D., Bondzic, A. M. & Vasic, V. M. (2013). Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. Current Neuropharmocology,11(3), 315-335.
https://doi.org/10.2174/1570159X11311030006
PMid:24179466 PMCid:PMC3648782

Darusman, L. K., Wahyuni, W. T., & Alwi, F. (2013). Acetylcholinesterase Inhibition and Antioxidant Activity of Syzygium cumini, S. aromaticum and S. polyanthum from Indonesia. Journal of Biological Sciences, 13(5), 412-416.
https://doi.org/10.3923/jbs.2013.412.416

Ellman, G .L., Courtney, D. K., Andreas, V. & Featherstone, R. M. (1961). A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity. Biochemical Pharmacology, 7, 88-95.
https://doi.org/10.1016/0006-2952(61)90145-9

Graham, W. V., Bonito-Oliva, A. & Sakmar, T. P., (2017). Update on Alzheimer's Disease Therapy and Prevention Strategies. Annual Review of Medicine, 68, 413-430.
https://doi.org/10.1146/annurev-med-042915-103753
PMid:28099083

Hadaginhal, R. V., Tikare, V. P., Patil, K. S., Bhanushali, M. D., Desai, N. S., & Karigar, A. (2010). Evaluation of Congnitive Enhancing Activity of Mimusops elengi linn on Albino Rats. International Journal of Research in Ayurveda & Pharmacy, 1(2), 484-492.

Hansen, R. A., Gartlehner, G., Webb, A. P., Morgan, L. C., Moore, C. G. & Jonas, D. E. (2008). Efficacy and Safety of Donepezil, Galantamine, and Rivastigmine for the Treatment of Alzheimer's Disease: A Systematic Review and Meta-analysis. Clinical Interventions in Aging, 3(2), 211-225.

Huang, H., Chen, W., Hsieh, R., & Hsieh-Li, H. M. (2014). Multifunctional Effects of Mangosteen Pericarp on Cognition in C57BL/6J and Triple Transgenic Alzheimer's Mice. Evidence-Based Complementary and Alternative Medicine, 2014, 1-18.
https://doi.org/10.1155/2014/813672
PMid:25525451 PMCid:PMC4267462

Ibrahim, M. Y., Hashim, N. M., Mohan, S., Abdulla, M. A., Abdelwahab, S. I., Arbab, I. A., . . . Ishag, O. E. (2015). α-Mangostin from Cratoxylum arborescens: An in vitro and in vivo Toxicological Evaluation. Arabian Journal of Chemistry, 8(1), 129-137.
https://doi.org/10.1016/j.arabjc.2013.11.017

Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P.C., & Tangalos, E. G. (1997). Medial Temporal Atrophy on MRI in Normal Aging and Very Mild Alzheimer's Disease. Neurology, 49, 786-794.
https://doi.org/10.1212/WNL.49.3.786
PMid:9305341 PMCid:PMC2730601

Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H. P. & Bussche, H. V. D. (2005). Cholinesterase inhibitors for patients with Alzheimer's disease: Systematic review of randomised clinical trials. BMJ, 331(321).
https://doi.org/10.1136/bmj.331.7512.321
PMid:16081444 PMCid:PMC1183129

Kumar, V., Bhatt, P. C., Kaithwas, G., Rashid, M., Al-Abbasi, F., Khan, J. A., . . . Verma, A. (2016). α-Mangostin Mediated Pharmacological Modulation of Hepatic Carbohydrate Metabolism in Diabetes Induced Wistar Rat. Beni-Suef University Journal of Basic and Applied Sciences, 5(3), 255-276.
https://doi.org/10.1016/j.bjbas.2016.07.001

Lawson, A. A. & Barr, R. D. (1987). Acetylcholinesterase in red blood cells. American Journal of Hematology, 26, 101.
https://doi.org/10.1002/ajh.2830260114

Li, G., Zhang, Y., Wu, P., Chen, N., Wu, Z., Yang, L., . . . Li, Y. (2015). New Phloroglucinol Derivatives from the Fruit Tree Syzygium jambos and Their Cytotoxic and Antioxidant Activities. Journal of Agricultural and Food Chemistry, 63(47), 10257-10262.
https://doi.org/10.1021/acs.jafc.5b04293
PMid:26554667

Mann, D. M. (1996). Pyramidal nerve cell loss in Alzheimer's disease. Neurodegeneration, 5, 423-427.
https://doi.org/10.1006/neur.1996.0057
PMid:9117557

Murugan, S., Uma Devi, P., Parameshwari, K. N., & Mani, K, R. (2011). Antimicrobial Activity of Syzygium jambos Against Selected Human Pathogens. International Journal of Pharmacy and Pharmaceutical Sciences, 2011(3), 44-47.

Nawwar, M., Hashem, A., Hussein, S., Swilam, N., Becker, A., Haertel, B., ... Linscheid, M. (2016). Phenolic Profiling of an Extract from Eugenia Jambos L. (Alston): The Structure of Three Flavonoid Glycosides-Antioxidant and Cytotoxic Activities. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 71, 162-168.

Norfray, J. F. & Provenzale, J. M. (2004). Alzheimer's Disease: Neuropathologic Findings and Recent Advances in Imaging. American Journal of Roentgenology, 182: 3-13.
https://doi.org/10.2214/ajr.182.1.1820003
PMid:14684506

Obolskiy, D., Pischel, I., Siriwatanametanon, N., Heinrich, M. (2009). Garcinia mangostana L.: A Phytochemical and Pharmacological Review. Phytotherapy Research, 23(8), 1047-1065.
https://doi.org/10.1002/ptr.2730
PMid:19172667

Povi, L., Batomayena, B., Hode, T. A., Kwashie, E., Kodjo, A., & Messanvi, G. (2015). Phytochemical Screening, Antioxidant and Hypoglycemic Activity of Coccoloba Uvifera Leaves and Waltheria Indica Roots Extracts. International Journal of Pharmacy and Pharmaceutical Sciences, 7(5), 279-283.

Prasad, V. K., Kavita, N. Y., Ramesh, S. D., Rakesh, S. S., & Manohar, J. P. (2012). Mimusops elengi: A Review on Ethnobotany, Phytochemical and Pharmacological Profile. Journal of Pharmacognosy and Phytochemistry, 1(3), 64-74.

Raghavendra, H., Kumar, S. P., Kekuda, T. P., R., Ejeta, E., Mulatu, K., . . . Anilakumar, K. (2011). Extraction and Evaluation of α-Mangostin for its Antioxidant and Acetylcholinesterase Inhibitory Activity. Journal of Biologically Active Products from Nature, 1(5 & 6), 314-324.
https://doi.org/10.1080/22311866.2011.10719099

RamLi, S., Radu, S., Shaari, K., & Rukayadi, Y. (2017). Antibacterial Activity of Ethanolic Extract of Syzygium polyanthum L. (Salam) Leaves against Foodborne Pathogens and Application as Food Sanitizer. BioMed Research International, 2017, 1-13.
https://doi.org/10.1155/2017/9024246
PMid:29410966 PMCid:PMC5749218

Sainiara,B., Jayashree, A., Archana, B., & Bratati, D. (2015). Chemical Composition and in vitro Study for Analysis of Potential Neuroprotective and Antidiabetic Activity in Mimusops elengi L. International Journal of Pharmacognosy and Phytochemical Research, 7(4), 701- 706.

Sattayasai, J., Chaonapan, P., Arkaravichie, T., Soi-Ampornkul, R., Junnu, S., Charoensilp, P. Moongkarndi, P. (2013). Protective Effects of Mangosteen Extract on H2O2-Induced Cytotoxicity in SK-N-SH Cells and Scopolamine-Induced Memory Impairment in Mice. PLoS ONE, 8(12). 1-13.
https://doi.org/10.1371/journal.pone.0085053
PMid:24386444 PMCid:PMC3874002

Selkoe, D. J. (2002). Alzheimer's disease is a synaptic failure. Science, 298, 89-91.
https://doi.org/10.1126/science.1074069
PMid:12399581

Shanmugapriya, P., Roziahanim, M., Piaru, S. P., Cai, L. W., & Surash, R. (2012). Potential Antiradical Activity and Cytotoxicity Assessment of Ziziphus mauritiana and Syzygium polyanthum. International Journal of Pharmacology, 8(6), 535-541.
https://doi.org/10.3923/ijp.2012.535.541

Sramek, J. J., Cutler, N. R. (2000). RBC Cholinesterase Ihibition: A Useful Surrogate Marker for Cholinesterase Inhibitor Activity in Alzheimer Disease Therapy? Alzheimer Disease and Associated Disorder, 14, 216-227. Alzheimer Disease and Associated Disorders
https://doi.org/10.1097/00002093-200010000-00006

Tang, Y., Li, P., Kondo, M., Ji, H., Kou, Y., & Ou, B. (2009). Effect of α-Mangosteen Dietary Supplement on Human Immune Function: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Medicinal Food, 12(4), 755-763.
https://doi.org/10.1089/jmf.2008.0204
PMid:19697997

Terry, A. V. & Buccafusco, J. J. (2003). The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development. Journal of Pharmacology and Experimental Therapeutics, 306(3), 821-827.
https://doi.org/10.1124/jpet.102.041616
PMid:12805474

Tjahjani, S., Widowati, W., Khiong, K., Suhendra, A., & Tjokropranoto, R. (2014). Antioxidant Properties of Garcinia Mangostana L. (Mangosteen) Rind. Procedia Chemistry, 13, 198-203.
https://doi.org/10.1016/j.proche.2014.12.027

Wang, B., Zhong, Y., Gao, C., & Li, J. (2017). Myricetin Ameliorates Scopolamine-Induced Memory Impairment in Mice via Inhibiting Acetylcholinesterase and Down-Regulating Brain Iron. Biochemical and Biophysical Research Communications, 490(2), 336-342.
https://doi.org/10.1016/j.bbrc.2017.06.045
PMid:28619513

Wang, M., Zhang, K., Gu, Q., Bi, X., & Wang, J. (2017). Pharmacology of Mangostins and Their Derivatives: A Comprehensive Review. Chinese Journal of Natural Medicines, 15(2), 81-93.
https://doi.org/10.1016/S1875-5364(17)30024-9

Widyawati, T., Yusoff, N., Asmawi, M., & Ahmad, M. (2015). Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats. Nutrients, 7(9), 7764-7780.
https://doi.org/10.3390/nu7095365
PMid:26389944 PMCid:PMC4586560