Generic placeholder image

Current Enzyme Inhibition

Editor-in-Chief

ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

Research Article

GC-MS Identification of Cholinesterase Inhibitory and Antioxidant Molecules from Leaves of Cnidoscolus aconitifolius (Miller) I.M. Johnston (Euphorbiaceae)

Author(s): Onoja Ojogbane Joel* and Ugwueze Nnamdi Joachin

Volume 19, Issue 1, 2023

Published on: 08 December, 2022

Page: [19 - 37] Pages: 19

DOI: 10.2174/1573408018666220324105559

Price: $65

Open Access Journals Promotions 2
Abstract

Backgound: Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disease, clinically characterized by memory and cognitive dysfunction. AD affects about 35 million people worldwide today and is estimated to nearly double every 20 years. Cnidoscolus aconitifolius (Miller) I.M. Johnston has been reported in Nigerian ethnomedicine as a memory enhancer. There is a lack of scientific evidence to justify the claims. Moreover, there are no effective neurotherapeutic agents available for the treatment of AD; hence the need arises to search for new and more effective agents.

Objective: This study aims to evaluate and identify potential molecules with anti-Alzheimer’s and antioxidant potentials from Cnidoscolus aconitifolius leaves.

Methods: The air-dried leaves of Cnidoscolus aconitifolius (Miller) I.M. Johnston (PCG/UNN/0267) were extracted using the successive extraction procedure based on increasing the polarity of the eluent in the ascending order of n-hexane, ethyl acetate, and methanol. Phytochemical screening was carried out on the extracts using standard procedures. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were done according to Ellman’s method. Eserine was used as standard. Antioxidant potentials were evaluated using standard in vitro chemical analyses. A GC-MS (QP2010SE, SHIDMAZU JAPAN) analysis was done to identify bioactive compounds from the most active fraction. Statistical analyses were performed using one-way ANOVA followed by Dunnett’s Multiple Comparison test at α0.05.

Results: Phytochemical analysis revealed the presence of tannins, resins, saponins, flavonoids, phenols, carbohydrates, alkaloids, and terpenoids. Ethyl acetate fraction demonstrated the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity at 1 mg/mL with IC50 values of 0.288 ± 0.00 mg/mL (82.9% inhibition) and 0.440±0.02 mg/mL ((75.4% inhibition), respectively, compared to eserine (IC50=0.050 ± 0.01 mg/mL) for AChE and (IC50=0.049 ± 0.00 mg/mL) for BuChE. Metal (ferrous ion) chelating activity was also high in the ethyl acetate fraction with IC50 value of 0.160 ± 0.00 mg/mL compared to EDTA (IC50 = 0.085 ± 0.00 mg/mL) at 1 mg/mL. Hydroxyl radical scavenging activity was higher in the ethyl acetate fraction (IC50 = 0.352 ± 0.01 mg/mL) when compared to BHT (IC50 = 0.074 ± 0.00 mg/mL) at 1 mg/mL. The pro-anthocyanidin content was also higher in ethyl acetate (6.94 ± 0.16 mg cyanidin/g of sample) compared to other fractions. GC-MS analysis of the most active fraction (ethyl acetate) revealed a total of 56 compounds. The major compounds revealed were: n-Hexadecanoic acid (Area % of 13.45%; Retention time of 14.863), Phytol (Area % of 5.13%; Retention time of 15.864), Octadecanoic acid (Area % of 4.86%; Retention time of 16.211), 9, 12, 15-Octadecatrienoic acid (Z,Z,Z) (Area % of 26.85%; Retention time of 16.09), Squalene (% Area of 2.65%; Retention time of 20.94) and alpha-Tocopheryl acetate (% Area of 1.71%; Retention time of 23.40).

Conclusion: C. aconitifolius has the potential to inhibit cholinesterase enzymes involved in the pathology of Alzheimer’s disease. The molecules identified could serve as potential drug leads in managing Alzheimer’s disease.

Keywords: Cnidoscolus aconitifolius, memory enhancing, metal chelating, GC-MS profiling, phytochemical analysis, Alzheimer’s disease.

Graphical Abstract
[1]
Donkoh A, Kese AG, Atuahene CC. Chemical composition of chaya leaf meal Cnidoscolus aconitifolius and availability of its amino acids to chicks. Anim Feed Sci Technol 1990; 30(1-2): 155-62.
[http://dx.doi.org/10.1016/0377-8401(90)90059-H]
[2]
Oyagbemi AA, Odetola AA, Azeez OI. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and osmotic fragility induced by protein energy malnutrition. Afr J Biotechnol 2008; 7(11): 1721-6.
[http://dx.doi.org/10.5897/AJB08.247]
[3]
Ross I, Molina C. The ethnobotany of Chaya Cnidoscolus aconitifolius ssp. Aconitifolius Breckon: A nutritious Maya vegetable. Econ Bot 2002; 56(4): 350-65.
[http://dx.doi.org/10.1663/0013-0001(2002)056[0350:TEOCCA]2.0.CO;2]
[4]
Atuahene CC, Poku-Prempeh B, Twun G. The nutritive values of Chaya leaf meal (Cnidoscolus aconitifolius): Studies with broilers chickens. Anim Feed Sci Technol 1999; 77(1-2): 163-72.
[http://dx.doi.org/10.1016/S0377-8401(98)00231-4]
[5]
Samuel I, Arthur N, Jude E, Henrietta C. Antihyperglycaemic efficacy of Cnidoscolus aconitifolius compared with glibenclamide in alloxan-induced diabetic Wistar rats. Int Res J Med Sci 2014; 2(3): 1-4.
[6]
Mordi JC. Antidiabetic potential of the aqueous leaf extract of Cnidoscolus aconitifolius on streptozotocin (STZ) induced diabetes in Wistar rat hepatocytes. Curr Res J Biol Sci 2012; 4(2): 164-7.
[7]
Azeez OI, Oyagbemi AA, Oyeyemi MO, Odetola AA. Ameliorative effects of Cnidoscolus aconitifolius on alloxan toxicity in Wistar rats. Afr Health Sci 2010; 10(3): 283-91.
[PMID: 21327141]
[8]
Oyagbemi AA, Odetola AA. Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage. Pharmacognosy Res 2013; 5(4): 260-4.
[http://dx.doi.org/10.4103/0974-8490.118817] [PMID: 24174819]
[9]
Adaramoye OA, Aluko A, Oyagbemi AA. Cnidoscolus aconitifolius leaf extract protects against hepatic damage induced by chronic ethanol administration in Wistar rats. Alcohol Alcohol 2011; 46(4): 451-8.
[http://dx.doi.org/10.1093/alcalc/agr060] [PMID: 21616948]
[10]
Obichi EA, Monago CC, Belonwu DC. Effect of Cnidoscolus aconitifolius (Family Euphorbiaceae) aqueous leaf extract on some antioxidant enzymes and haematological parameters of high fat diet and streptozotocin induced diabetic wistar albino rats. J Appl Sci Environ Manag 2015; 19(1): 201-9.
[http://dx.doi.org/10.4314/jasem.v19i2.5]
[11]
Onasanwo SA, Oyagbemi AA, Saba AB. Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice. J Basic Clin Physiol Pharmacol 2011; 22(1-2): 37-41.
[http://dx.doi.org/10.1515/jbcpp.2011.010] [PMID: 22865362]
[12]
Skovronsky DM, Lee VMY, Trojanowski JQ. Neurodegenerative diseases: New concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol 2006; 1(1): 151-70.
[http://dx.doi.org/10.1146/annurev.pathol.1.110304.100113] [PMID: 18039111]
[13]
Mayeux R. Epidemiology of neurodegeneration. Annu Rev Neurosci 2003; 26(1): 81-104.
[http://dx.doi.org/10.1146/annurev.neuro.26.043002.094919] [PMID: 12574495]
[14]
Ferri CP, Sousa R, Albanese E, Ribeiro WS, Honyashiki M. World Alzheimer’s Report 2009- Executive Summary London: Alzheimer’s Disease International 2009; pp. 1-22.
[15]
Kamal MA, Al-Jafari AA, Yu QS, Greig NH. Kinetic analysis of the inhibition of human butyrylcholinesterase with cymserine. Biochim Biophys Acta 2006; 1760(2): 200-6.
[http://dx.doi.org/10.1016/j.bbagen.2005.10.003] [PMID: 16309845]
[16]
Ellis JM. Cholinesterase inhibitors in the treatment of dementia. J Am Osteopath Assoc 2005; 105(3): 145-58.
[PMID: 15863734]
[17]
Henry W, Querfurth HW, LaFerla FM. Mechanisms of disease Alzheimer’s disease. N Engl J Med 2010; 362(4): 329-44.
[http://dx.doi.org/10.1056/NEJMra0909142]
[18]
Heleno SA, Barros L, Martins A, Queiroz MJRP, Santos-Buelga C, Ferreira ICFR. Fruiting body, spores and in vitro produced mycelium of Ganoderma lucidum from Northeast Portugal: A comparative study of the antioxidant potential of phenolic and polysaccharidic extracts. Food Res Int 2012; 46(1): 135-40.
[http://dx.doi.org/10.1016/j.foodres.2011.12.009]
[19]
Zhao Y, Dou J, Wu T, Aisa HA. Investigating the antioxidant and acetylcholinesterase inhibition activities of Gossypium herbaceam. Molecules 2013; 18(1): 951-62.
[http://dx.doi.org/10.3390/molecules18010951] [PMID: 23344203]
[20]
Bartus RT, Dean RL III, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217(4558): 408-14.
[http://dx.doi.org/10.1126/science.7046051] [PMID: 7046051]
[21]
Farrimond LE, Roberts E, McShane R. Memantine and cholinesterase inhibitor combination therapy for Alzheimer’s disease: A systematic review. BMJ 2012; 2e000917
[http://dx.doi.org/10.1136/bmjopen-2012-000917]
[22]
Van der zee EA, Platt B, Riedel G. Acetylcholine: Future research and perspectives. Behav Brain Res 2012; 221(2): 583-6.
[PMID: 21295616]
[23]
Perez LR, Franz KJ. Minding metals: Tailoring multifunctional chelating agents for neurodegenerative disease. Dalton Trans 2010; 39(9): 2177-87.
[http://dx.doi.org/10.1039/B919237A] [PMID: 20162187]
[24]
Abulude FO. Phytochemical screening and mineral contents of leaves of some Nigerian woody plants. Res J Phytochem 2007; 1(1): 33-9.
[http://dx.doi.org/10.3923/rjphyto.2007.33.39]
[25]
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7(2): 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[26]
Singh N, Rajini PS. Free radical scavenging activity of an aqueous extract of potato peel. Food Chem 2004; 85(4): 611-6.
[http://dx.doi.org/10.1016/j.foodchem.2003.07.003]
[27]
Halliwell B, Gutteridge JM, Aruoma OI. The deoxyribose method: A simple “test-tube” assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem 1987; 165(1): 215-9.
[http://dx.doi.org/10.1016/0003-2697(87)90222-3] [PMID: 3120621]
[28]
Porter LJ, Hrstich LN, Chan BG. The conversion of procyanidins and prodelphinidins to cyanidin and delphinidin. Phytochemistry 1986; 25(1): 223-30.
[http://dx.doi.org/10.1016/S0031-9422(00)94533-3]
[29]
Shay PE, Peter CC, Trofymow JA. Evidence for the role and fate of water-insoluble condensed tannins in the short term reduction of carbon loss during litter decay. Biogeochemistry 2017; 137(1-2): 127-41.
[http://dx.doi.org/10.1007/s10533-017-0406-x]
[30]
Liu W, Liu J, Yin D, Zhao X. Influence of ecological factors on the production of active substances in the anti-cancer plant Sinopodophyllum hexandrum (Royle) T.S. Ying. PLoS One 2015; 10(4)e0122981
[http://dx.doi.org/10.1371/journal.pone.0122981] [PMID: 25874701]
[31]
Otitolaiye CA, Asokan C. GC-MS analysis of Cnidoscolus aconitifolius leaf aqueous extracts. Int J Sci Res 2015; 5(8): 2319-7064.
[32]
Ferreira MP, Gendron F, McClure KC, Kindscher K. North American bioactive plants for human health & performance. Glob J Res Med Plants Indig Med 2012; 1(11): 568-82.
[33]
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009; 2(5): 270-8.
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[34]
Greig NH, Lahiri DK, Sambamurti K. Butyrylcholinesterase: An important new target in Alzheimer’s disease therapy. Int Psychogeriatr 2002; 14(S1) (Suppl. 1): 77-91.
[http://dx.doi.org/10.1017/S1041610203008676] [PMID: 12636181]
[35]
Ata A, Iverson CD, Kalhari KS, Akhter S. Bettteridge, Meshkatalsadat, M.H. Triterpenoid alkaloids from Buxus hyrcana and their enzyme inhibitory, anti-fungal and anti-leishmanial activities. Phytochemistry 2010; 71: 1780-6.
[http://dx.doi.org/10.1016/j.phytochem.2010.06.017] [PMID: 20655557]
[36]
Zatta P, Drago D, Bolognin S, Sensi SL. Alzheimer’s disease, metal ions and metal homeostatic therapy. Trends Pharmacol Sci 2009; 30(7): 346-55.
[http://dx.doi.org/10.1016/j.tips.2009.05.002] [PMID: 19540003]
[37]
Zheng H, Gal S, Weiner LM, et al. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: In vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J Neurochem 2005; 95(1): 68-78.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03340.x] [PMID: 16181413]
[38]
Derzieve C, Pitie M, Mazarguil H. Meunier, B. Bis-8-hydroxyquinoline ligands as potential anti-Alzheimer agents. New J Chem 2007; 31: 193-5.
[http://dx.doi.org/10.1039/b616085a]
[39]
Zheng H, Youdim MBH, Weiner LM, Fridkin M. Synthesis and evaluation of peptidic metal chelators for neuroprotection in neurodegenerative diseases. J Pept Res 2005; 66(4): 190-203.
[http://dx.doi.org/10.1111/j.1399-3011.2005.00289.x] [PMID: 16138857]
[40]
Bashiru OA, Oluwafemi AO, Mary AO, Babatunji EO, Abidemi PO. Ethyl acetate leaf fraction of Cnidoscolus aconitifolius (Mill.) I.M. Johnst: Antioxidant potential, inhibitory activities of key enzymes on carbohydrate metabolism, cholinergic, monoaminergic, purinergic and chemical fingerprinting. Int J Food Prop 2018; 21(1): 1697-715.
[http://dx.doi.org/10.1080/10942912.2018.1504787]
[41]
William CE. 16th ed Trease and Evans Pharmacognosy, Amsterdam: Elsevier 2009; pp. 225-347.
[42]
Ashutosh K. Glycosides. 3rd ed. Pharmacognosy and Pharmaco Biotechnology; USA: Williams and Wilkins 2018; p. 168.
[43]
Milena MRR, Jorge CMO, Mariana GD, Diana KBA. Use of Chaya (Cnidoscolus chayamansa) leaves for nutritional compounds production for human consumption. J Mex Chem Soc 2021; 65(1): 1870-249X.
[44]
Sermakkani M, Thangapandian V. GC-MS analysis of Cassia italica leaf methanol extract Asian J Pharm Clin Res 2012; 5(2): 0974-2441.
[45]
Olaoluwa O, Moronkola D, Taiwo O, Iganboh P. Volatile oil composition, antioxidant and antimicrobial properties of Boerhavia erecta L. and Euphorbia hirta L. Trends in Phytochem Res 2018; 2: 171-8.
[46]
Krishna ANV, Raman BV, Babu KR, Apparao C. Antioxidant activity and GC-MS analysis of Phragmytes vallatoria leaf ethanoic extract. Int Res J Pharm 2012; 3: 252-4.
[47]
Tian C, Gao X, Yang J, Gua Y, Wang H, Liu M. Chemical compositions, extraction technology and antioxidant activity of petroleum ether extract from Abutilon theophrasti Medic. Leaves. Int J Food Prop 2018; 21(1): 1789-99.
[http://dx.doi.org/10.1080/10942912.2018.1494198]
[48]
Aparna V, Dileep KV, Mandal PK, Karthe P, Sadasivan C, Haridas M. Anti-inflammatory property of n-hexadecanoic acid: Structural evidence and kinetic assessment. Chem Biol Drug Des 2012; 80(3): 434-9.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01418.x] [PMID: 22642495]
[49]
Korbecki J, Bajdak-Rusinek K. The effect of palmitic acid on inflammatory response in macrophages: An overview of molecular mechanisms. Inflamm Res 2019; 68(11): 915-32.
[http://dx.doi.org/10.1007/s00011-019-01273-5] [PMID: 31363792]
[50]
Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N Engl J Med 1997; 336(17): 1216-22.
[http://dx.doi.org/10.1056/NEJM199704243361704] [PMID: 9110909]
[51]
Hamid AA, Oguntoye SO, Negi AS, Ajao AO, Nurudeen O. Chemical constituents, antibacterial, antifungal and antioxidant activities of the aerial parts of Cnidoscolus aconitifolius. Ife J Sci 2016; 18: 2.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy