In vitro anti-cholinesterase activity and in vivo screening of Coccoloba uvifera, Mimusops elengi and Syzygium aqueum extracts on learning and memory function of chronic cerebral hypoperfusion rat
DOI:
https://doi.org/10.31117/neuroscirn.v4i2.71Keywords:
Chronic cerebral hypoperfusion, vascular dementia, anti-cholinesterase, Mimusops elengi, Syzygium aqueumAbstract
Vascular dementia (VaD), is one of the most common types of dementia in the ageing population, initiated by chronic cerebral hypoperfusion (CCH). At present, effective therapeutic approaches to cure VaD are still missing. Cholinergic system dysfunction in the central nervous system (CNS) has been recognised as one of the main reasons for learning and memory impairment in VaD patients. Therefore, medications that restore the level of acetylcholine (ACh) neurotransmitter by inhibiting cholinesterase activity were proposed as a potential candidate to treat VaD patients. Permanent occlusion of bilateral common carotid arteries (POBCCA) surgery method was performed to develop CCH model in rats. The present study evaluated the anti-cholinesterase activity of three Malaysian plant methanol leaf extracts in vitro and further validated its cognitive-enhancing effects in vivo using POBCCA rats. The selected plant extracts were Coccoloba uvifera (stems), Mimusops elengi (leaves) and Syzygium aqueum (leaves). The in vitro anti-cholinesterase activities of these plants were determined using Ellman's method. The effects of selected plant extracts (100 and 200 mg/kg, p.o.) on learning and memory functions were evaluated using a series of behavioural tests. All the selected plant extracts exhibited good anti-acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in vitro, with IC50 ranging from 3.67 to 16.04 and 5.6 to 13.95 µg/mL, respectively. Extracts of S. aqueum (200 mg/kg) improve both short- and long-term recognition memories, whereas M. elengi and S. aqueum (200 mg/kg) extracts improve spatial learning. None of the extracts impaired motor and exploratory functions in POBCCA rats. In conclusion, methanol extracts of C. uvifera, M. elengi and S. aqueum showed good anti-cholinesterase activity in vitro. However, only M. elengi and S. aqueum improve learning and memory function in POBCCA rats.
References
Ahad, M. A., Kumaran, K. R., Ning, T., Mansor, N. I., Effendy, M. A., Damodaran, T., Lingam, K., Wahab, H. A., Nordin, N., Liao, P., Müller, C. P., & Hassan, Z. (2020). Insights into the neuropathology of cerebral ischemia and its mechanisms. Reviews in the Neurosciences, 31(5), 521–538. https://doi.org/10.1515/revneuro-2019-0099
Amenta, F., Di Tullio, M. A., & Tomassoni, D. (2002). The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies. Clinical and Experimental Hypertension, 24(7-8), 697–713. https://doi.org/10.1081/ceh-120015346
Amir Rawa, M. S., Hassan, Z., Murugaiyah, V., Nogawa, T., & Wahab, H. A. (2019). Anti-cholinesterase potential of diverse botanical families from Malaysia: Evaluation of crude extracts and fractions from liquid-liquid extraction and acid-base fractionation. Journal of Ethnopharmacology, 245, 112160. https://doi.org/10.1016/j.jep.2019.112160
Antunes, M., & Biala, G. (2012). The novel object recognition memory: neurobiology, test procedure, and its modifications. Cognitive Processing, 13(2), 93–110. https://doi.org/10.1007/s10339-011-0430-z
Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E. M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E. H., Rollinger, J. M., Schuster, D., Breuss, J. M., Bochkov, V., Mihovilovic, M. D., Kopp, B., Bauer, R., Dirsch, V. M., & Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33(8), 1582–1614. https://doi.org/10.1016/j.biotechadv.2015.08.001
Azam, N. F., Stanyard, R. A., Mat, N. H., & Hassan, Z. (2018). Cholinergic modulation of hippocampal long-term potentiation in chronic cerebral hypoperfused rats. Neuroscience Research Notes, 1(1), 42–57. https://doi.org/10.31117/neuroscirn.v1i1.15
Ballinger, E. C., Ananth, M., Talmage, D. A., & Role, L. W. (2016). Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron, 91(6), 1199–1218. https://doi.org/10.1016/j.neuron.2016.09.006
Cohen, S. J., Munchow, A. H., Rios, L. M., Zhang, G., Asgeirsdóttir, H. N., & Stackman, R. W., Jr (2013). The rodent hippocampus is essential for non-spatial object memory. Current Biology, 23(17), 1685–1690. https://doi.org/10.1016/j.cub.2013.07.002
Damodaran, T., Hassan, Z., Navaratnam, V., Muzaimi, M., Ng, G., Müller, C. P., Liao, P., & Dringenberg, H. C. (2014). Time course of motor and cognitive functions after chronic cerebral ischemia in rats. Behavioural Brain Research, 275, 252–258. https://doi.org/10.1016/j.bbr.2014.09.014
Duong, S., Patel, T., & Chang, F. (2017). Dementia: What pharmacists need to know. Canadian Pharmacists Journal/Revue des Pharmaciens du Canada, 150(2), 118–129. https://doi.org/10.1177/1715163517690745
Farkas, E., Luiten, P. G., & Bari, F. (2007). Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Research Reviews, 54(1), 162–180. https://doi.org/10.1016/j.brainresrev.2007.01.003
Hu, Y., Yang, Y., Zhang, M., Deng, M., & Zhang, J. J. (2017). Intermittent fasting pretreatment prevents cognitive impairment in a rat model of chronic cerebral hypoperfusion. The Journal of Nutrition, 147(7), 1437–1445. https://doi.org/10.3945/jn.116.245613
Institoris, A., Farkas, E., Berczi, S., Sule, Z., & Bari, F. (2007). Effects of cyclooxygenase (COX) inhibition on memory impairment and hippocampal damage in the early period of cerebral hypoperfusion in rats. European Journal of Pharmacology, 574(1), 29–38. https://doi.org/10.1016/j.ejphar.2007.07.019
Ivanco, T. L., & Racine, R. J. (2000). Long-term potentiation in the reciprocal corticohippocampal and corticocortical pathways in the chronically implanted, freely moving rat. Hippocampus, 10(2), 143–152. https://doi.org/10.1002/(SICI)1098-1063(2000)10:2<143::AID-HIPO3>3.0.CO;2-G
Jana, G. K., Dhanamjayarao, M., & Vani, M. (2010). Evaluation of anthelmintic potential of Mimusops elengi linn. (Sapotaceae) leaf. Journal of Pharmacy Research, 3(10), 2514‐ 2515.
Jellinger, K. A. (2013). Pathology and pathogenesis of vascular cognitive impairment-a critical update. Frontiers in Aging Neuroscience, 5, 17. https://doi.org/10.3389/fnagi.2013.00017
Jia, Z., Guo, Y., Tang, Y., Xu, Q., Li, B., & Wu, Q. (2014). Regulation of the protocadherin Celsr3 gene and its role in globus pallidus development and connectivity. Molecular and Cellular Biology, 34(20), 3895–3910. https://doi.org/10.1128/MCB.00760-14
Joshi, H., & Parle, M. (2012). Reversal of memory deficits by ethanolic extract of Mimusops elengi Linn. in mice. Pharmacognosy Journal, 4(29), 30-39. https://doi.org/10.5530/pj.2012.29.5
Karmakar, U. K., Sultana, R., & Biswas, N. N. (2011). Antioxidant, analgesic and cytotoxic activities of Mimusops elengi linn. Leaves. International Journal of Pharmaceutical Sciences and Research, 2(11), 2791‐2797. http://dx.doi.org/10.13040/IJPSR.0975-8232.2(11).2791-97
Khan, A., Kalaria, R. N., Corbett, A., & Ballard, C. (2016). Update on Vascular Dementia. Journal of Geriatric Psychiatry and Neurology, 29(5), 281–301. https://doi.org/10.1177/0891988716654987
Khatri, D. K., Manjulakonka, & Juvekar, A. R. (2014). Evaluation of Anti-inflammatory activity of Mimusops elengi extracts in different in-vitro and in-vivo models. International Journal of Pharmacy and Biological Sciences, 5(1), 259-268.
Kim, S. H., Kang, H. S., Kim, H. J., Moon, Y., Ryu, H. J., Kim, M. Y., & Han, S. H. (2012). The effect of ischemic cholinergic damage on cognition in patients with subcortical vascular cognitive impairment. Journal of Geriatric Psychiatry and Neurology, 25(2), 122–127. https://doi.org/10.1177/0891988712445089
Kitamura, A., Fujita, Y., Oishi, N., Kalaria, R. N., Washida, K., Maki, T., Okamoto, Y., Hase, Y., Yamada, M., Takahashi, J., Ito, H., Tomimoto, H., Fukuyama, H., Takahashi, R., & Ihara, M. (2012). Selective white matter abnormalities in a novel rat model of vascular dementia. Neurobiology of Aging, 33(5), 1012.e25–1012.e1.012E35. https://doi.org/10.1016/j.neurobiolaging.2011.10.033
Kumaran, K. R., Ahad, M., Rawa, M., Wahab, H., & Hassan, Z. (2019). Potential Malaysian medicinal plants for the treatment of Alzheimer's disease. Australian Herbal Insight, 1(4), 022-027. https://doi.org/10.25163/ahi.110006
Kurz, A. F. (2001). What is vascular dementia?. International Journal of Clinical Practice. Supplement, (120), 5–8
Lee, B., Choi, E. J., Lee, E. J., Han, S. M., Hahm, D. H., Lee, H. J., & Shim, I. (2011). The neuroprotective effect of methanol extract of gagamjungjihwan and fructus euodiae on ischemia-induced neuronal and cognitive impairment in the rat. Evidence-based Complementary and Alternative Medicine : eCAM, 2011, 685254. https://doi.org/10.1093/ecam/nep028
Lobo, A., Launer, L. J., Fratiglioni, L., Andersen, K., Di Carlo, A., Breteler, M. M., Copeland, J. R., Dartigues, J. F., Jagger, C., Martinez-Lage, J., Soininen, H., & Hofman, A. (2000). Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology, 54(11), S4–S9.
MacDonald, C. J., Carrow, S., Place, R., & Eichenbaum, H. (2013). Distinct hippocampal time cell sequences represent odor memories in immobilised rats. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33(36), 14607–14616. https://doi.org/10.1523/JNEUROSCI.1537-13.2013
Mehta, A. (2018). Storing and retrieving long-term memories: Cooperation and competition in synaptic dynamics. Advances in Physics: X, 3(1), 756-790. https://doi.org/10.1080/23746149.2018.1480415
Moretti, A., Gorini, A., & Villa, R. F. (2011). Pharmacotherapy and prevention of vascular dementia. CNS & Neurological Disorders Drug Targets, 10(3), 370–390. https://doi.org/10.2174/187152711794653832
Narayanaswamy, N., Rohini, S., Duraisamy, A., & Balakrishnan, K. P. (2011). Antityrosinase and antioxidant activities of various parts of Mimusops elengi: a comparative study. International Journal of Research in Cosmetic Science, 1(1), 17-22.
Noufi, P., Khoury, R., Jeyakumar, S., & Grossberg, G. T. (2019). Use of Cholinesterase Inhibitors in Non-Alzheimer's Dementias. Drugs & Aging, 36(8), 719–731. https://doi.org/10.1007/s40266-019-00685-6
Okada, K., Nishizawa, K., Kobayashi, T., Sakata, S., & Kobayashi, K. (2015). Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory. Scientific Reports, 5, 13158. https://doi.org/10.1038/srep13158
Osman, H., Rahim, A. A., Isa, N. M., & Bakhir, N. M. (2009). Antioxidant activity and phenolic content of Paederia foetida and Syzygium aqueum. Molecules (Basel, Switzerland), 14(3), 970–978. https://doi.org/10.3390/molecules14030970
Palanisamy, U. D., Ling, L. T., Manaharan, T., Sivapalan, V., Subramaniam, T., Helme, M. H., & Masilamani, T. (2011). Standardised extract of Syzygium aqueum: a safe cosmetic ingredient. International Journal of Cosmetic Science, 33(3), 269–275. https://doi.org/10.1111/j.1468-2494.2010.00637.x
Palanisamy, U., & Manaharan, T. (2015). Syzygium aqueum leaf extracts for possible anti-diabetic treatment. Acta Horticulturae, 1098, 13-22. https://doi.org/10.17660/ActaHortic.2015.1098.1
Panda, S. S., & Jhanji, N. (2020). Natural Products as Potential Anti-Alzheimer Agents. Current medicinal chemistry, 27(35), 5887–5917. https://doi.org/10.2174/0929867326666190618113613
Pantoni, L. (2004). Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. Journal of the neurological sciences, 226(1-2), 67–70. https://doi.org/10.1016/j.jns.2004.09.014.
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
Qu, C., Song, H., Shen, J., Xu, L., Li, Y., Qu, C., Li, T., & Zhang, J. (2020). Mfsd2a reverses spatial learning and memory impairment caused by chronic cerebral hypoperfusion via protection of the blood-brain barrier. Frontiers in Neuroscience, 14(461), 1-9. https://doi.org/10.3389/fnins.2020.00461.
Satishchandra, A., & Sumithra, M. (2011). Synergistic effect of Mimusops elengi and moringa oleifera on high fat diet induced atheroma in rats. International Journal of Advances in Pharmaceutical Research, 2(6), 293–300.
Román, G. C. (2002). Vascular dementia may be the most common form of dementia in the elderly. Journal of the Neurological Sciences, 203-204, 7–10. https://doi.org/10.1016/s0022-510x(02)00252-6
Saxena, A. K., Abdul-Majeed, S. S., Gurtu, S., & Mohamed, W. M. (2015). Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats. Applied & Translational Genomics, 5, 30–32. https://doi.org/10.1016/j.atg.2015.05.004
Snyder, H. M., Corriveau, R. A., Craft, S., Faber, J. E., Greenberg, S. M., Knopman, D., Lamb, B. T., Montine, T. J., Nedergaard, M., Schaffer, C. B., Schneider, J. A., Wellington, C., Wilcock, D. M., Zipfel, G. J., Zlokovic, B., Bain, L. J., Bosetti, F., Galis, Z. S., Koroshetz, W., & Carrillo, M. C. (2015). Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimer's & Dementia : the Journal of the Alzheimer's Association, 11(6), 710–717. https://doi.org/10.1016/j.jalz.2014.10.008
Sobeh, M., Mahmoud, M. F., Petruk, G., Rezq, S., Ashour, M. L., Youssef, F. S., El-Shazly, A. M., Monti, D. M., Abdel-Naim, A. B., & Wink, M. (2018). Syzygium aqueum: A polyphenol- rich leaf extract exhibits antioxidant, hepatoprotective, pain-killing and anti-inflammatory activities in animal models. Frontiers in Pharmacology, 9(566), 1-14. https://doi.org/10.3389/fphar.2018.00566
Sohn, E., Kim, Y. J., Lim, H. S., Kim, B. Y., & Jeong, S. J. (2019). Hwangryunhaedok-tang exerts neuropreventive effect on memory impairment by reducing cholinergic system dysfunction and inflammatory response in a vascular dementia rat model. Molecules, 24(2), 343. https://doi.org/10.3390/molecules24020343
Tiang, N., Ahad, M. A., Murugaiyah, V., & Hassan, Z. (2020). Xanthone-enriched fraction of garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats. Journal of Pharmacy and Pharmacology, 72(11), 1629-1644. https://doi.org/10.1111/jphp.13345
Vijayan, M., & Reddy, P. H. (2016). Stroke, Vascular Dementia, and Alzheimer's Disease: Molecular Links. Journal of Alzheimer's disease, 54(2), 427–443. https://doi.org/10.3233/JAD-160527
Vorhees, C. V., & Williams, M. T. (2006). Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2), 848–858. https://doi.org/10.1038/nprot.2006.116
Wang, J., Zhang, H. Y., & Tang, X. C. (2009). Cholinergic deficiency involved in vascular dementia: Possible mechanism and strategy of treatment. Acta Pharmacologica Sinica, 30(7), 879–888. https://doi.org/10.1038/aps.2009.82
Williams, B., Watanabe, C. M., Schultz, P. G., Rimbach, G., & Krucker, T. (2004). Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability. Neurobiology of Aging, 25(7), 955–962. https://doi.org/10.1016/j.neurobiolaging.2003.10.008
Yao, Z., Yao, X., Zhang, S., Hu, J., & Zhang, Y. (2019). Tripchlorolide may improve spatial cognition dysfunction and synaptic plasticity after chronic cerebral hypoperfusion. Neural Plasticity, 2019, 1-14. https://doi.org/10.1155/2019/2158285
Zahid, H., Rizwani, G. H., Shareef, H., Mahmud, S., & Ali, T. (2012). Hypoglycemic and hypolipidemic effects of Mimusops elengi Linn, extracts on normoglycaemic and alloxan-induced diabetic rats. International Journal of Pharmaceutical and Biological Archives, 3(1), 56-62.
Zlokovic, B. V. (2005). Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends in Neurosciences, 28(4), 202–208. https://doi.org/10.1016/j.tins.2005.02.001
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