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http://dx.doi.org/10.47853/FAS.2022.e6

Cholinesterase inhibitory activities of neuroprotective fraction derived from red alga Gracilaria manilaensis  

Pang, Jun-Rui (Department of Biological Sciences, School of Medical and Life Sciences, Sunway University)
How, Sher-Wei (Department of Molecular Medicine and Pathology, Faculty of Medical and Health Science, The University of Auckland)
Wong, Kah-Hui (Department of Anatomy, Faculty of Medicine, Universiti Malaya)
Lim, Siew-Huah (Department of Chemistry, Faculty of Sciences, Universiti Malaya)
Phang, Siew-Moi (Faculty of Applied Sciences, UCSI University)
Yow, Yoon-Yen (Department of Biological Sciences, School of Medical and Life Sciences, Sunway University)
Publication Information
Fisheries and Aquatic Sciences / v.25, no.2, 2022 , pp. 49-63 More about this Journal
Abstract
Anti-cholinesterase (ChE)s are commonly prescribed as the symptomatic treatment of Alzheimer's disease. They are applied to prevent the breakdown of neurotransmitter acetylcholine (ACh) that bind to muscarinic and nicotinic receptors in the synaptic cleft. Seaweeds are one of the richest sources of bioactive compounds for both nutraceuticals and pharmacognosy applications. This study aimed to determine the anti-ChEs activity of Gracilaria manilaensis, one of the red seaweeds notables for its economic importance as food and raw materials for agar production. Methanol extracts (GMM) of G. manilaensis were prepared through maceration, and further purified with column chromatography into a semi-pure fraction. Ellman assay was carried out to determine the anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activities of extracts and fractions. Lineweaver-Burk plot analysis was carried out to determine the inhibition kinetic of potent extract and fraction. Major compound(s) from the most potent fraction was determined by liquid chromatography-mass spectrometry (LCMS). GMM and fraction G (GMMG) showed significant inhibitory activity AChE with EC50 of 2.6 mg/mL and 2.3 mg/mL respectively. GMM and GMMG exhibit mixed-inhibition and uncompetitive inhibition respectively against AChE. GMMG possesses neuroprotective compounds such as cynerine A, graveolinine, militarinone A, eplerenone and curumenol. These findings showed a promising insight of G. manilaensis to be served as a nutraceutical for neuronal health care in the future.
Keywords
Gracilaria manilaensis; Alzheimer's disease; Graveolinine; Mixed-inhibition; Uncompetitive inhibition; Cholinesterases;
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1 Loizzo MR, Bonesi M, Nabavi SM, Sobarzo-Sanchez E, Rastrelli L, Tundis R, et al. Hypoglycaemic effects of plants food constituents via inhibition of carbohydrate-hydrolysing enzymes: from chemistry to future applications. In: Andrade PB, Valentao P, Pereira DM, editors. Natural products targeting clinically relevant enzymes. Weinheim, Germany: Wiley-VCH; 2017. p 135-53.
2 Lombardo S, Maskos U. Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment. Neuropharmacology. 2015;96:255-62.   DOI
3 Machado LP, Carvalho LR, Young MCM, Cardoso-Lopes EM, Centeno DC, Zambotti-Villela L, et al. Evaluation of acetylcholinesterase inhibitory activity of Brazilian red macroalgae organic extracts. Rev Bras Farmacogn. 2015;25:657-62.   DOI
4 Marcotullio MC, Mwankie GNO-M, Cossignani L, Tirillini B, Pagiotti R. Phytochemical analysis and antiradical properties of Sarcodon imbricatus (L.:Fr) Karsten. Nat Prod Commun. 2008;3:1907-10.
5 Wang X, Zhu Y, Wang S, Wang Z, Sun H, He Y, et al. Effects of eplerenone on cerebral aldosterone levels and brain lesions in spontaneously hypertensive rats. Clin Exp Hypertens. 2020;42:531-8.   DOI
6 Mielke MM, Leoutsakos JM, Corcoran CD, Green RC, Norton MC, Welsh-Bohmer KA, et al. Effects of food and drug administration-approved medications for Alzheimer's disease on clinical progression. Alzheimers Dement. 2012;8:180-7.   DOI
7 Phang SM, Yeong HY, Lim PE. The seaweed resources of Malaysia. Bot Mar. 2019;62:265-73.   DOI
8 Pintatum A, Maneerat W, Logie E, Tuenter E, Sakavitsi ME, Pieters L, et al. In vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species and the isolation of compounds from Curcuma aromatica rhizome. Biomolecules. 2020;10:799.   DOI
9 Riese U, Ziegler E, Hamburger M. Militarinone A induces differentiation in PC12 cells via MAP and Akt kinase signal transduction pathways. FEBS Lett. 2004;577:455-9.   DOI
10 Reid T, Kashangura C, Chidewe C, Benhura MA, Stray-Pedersen B, Mduluza T, et al. Characterization of anti-Salmonella typhi compounds from medicinal mushroom extracts from Zimbabwe. Int J Med Mushrooms. 2019;21:713-24.   DOI
11 Bagheri E, Hajiaghaalipour F, Nyamathulla S, Salehen NA. Ethanolic extract of Brucea javanica inhibit proliferation of HCT-116 colon cancer cells via caspase activation. RSC Advances. 2018;8:681-9.   DOI
12 Ruangritchankul S, Chantharit P, Srisuma S, Gray LC. Adverse drug reactions of acetylcholinesterase inhibitors in older people living with dementia: a comprehensive literature review. Ther Clin Risk Manag. 2021;17:927-49.   DOI
13 Chen H, Sun F, Zhong X, Shao Y, Yoshimura A, Liu Y, et al. Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing renal inflammation, interstitial cell proliferation and oxidative stress. Kidney Blood Press Res. 2013;37:557-66.   DOI
14 Hamdi OAA, Ye LJ, Kamarudin MNA, Hazni H, Paydar M, Looi CY, et al. Neuroprotective and antioxidant constituents from Curcuma zedoaria rhizomes. Rec Nat Prod. 2015;9:349-55.
15 Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia. Clin Interv Aging. 2017;12:697-707.   DOI
16 Luo W, Lv JW, Wang T, Zhang ZY, Guo HY, Song ZY, et al. Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer's agents. Bioorg Med Chem. 2020;28:115190.   DOI
17 McGinty D, Letizia CS, Api AM. Fragrance material review on (2E,6Z)-nona-2,6-dien-1-ol. Food Chem Toxicol. 2010;48:S91-2.   DOI
18 Tsuno N. Donepezil in the treatment of patients with Alzheimer's disease. Expert Rev Neurother. 2009;9:591-8.   DOI
19 Wang B, Han J, Xu W, Chen Y, Liu, H. Production of bioactive cyathane diterpenes by a bird's nest fungus Cyathus gansuensis growing on cooked rice. Food Chem. 2014;152:169-76.   DOI
20 World Health Organisation. Dementia. 2021 [cited 2021 Aug 21]. https://www.who.int/news-room/fact-sheets/detail/dementia
21 Wu TS, Shi LS, Wang JJ, Iou SC, Chang HC, Chen YP, et al. Cytotoxic and antiplatelet aggregation principles of Ruta graveolens. J Chin Chem Soc. 2003;50:171-8.   DOI
22 Yoon NY, Chung HY, Kim HR, Choi JE. Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera. Fish Sci. 2008;74:200-7.   DOI
23 Yoon NY, Lee SH, Yong-Li, Kim SK. Phlorotannins from Ishige okamurae and their acetyl- and butyrylcholinesterase inhibitory effects. J Funct Foods. 2009;1:331-5.   DOI
24 Silverthorn DU. Neruons: Cellular and network properties. In: Human Physiology: An Integrated Approach. London: Pearson; 2016. p. 277-84.
25 Andriani Y, Syamsumir DF, Yee TC, Harisson FS, Herng GM, Abdullah SA, et al. Biological activities of isolated compounds from three edible Malaysian red seaweeds, Gracilaria changii, G. manilaensis and Gracilaria sp. Nat Prod Commun. 2016;11:1117-20.
26 Obara Y, Hoshino T, Marcotullio MC, Pagiotti R, Nakahata N. A novel cyathane diterpene, cyrneine A, induces neurite outgrowth in a Rac1-dependent mechanism in PC12 cells. Life Sci. 2007;80:1669-77.   DOI
27 Pang JR, Goh VMJ, Tan CY, Phang SM, Wong KH, Yow YY, et al. Neuritogenic and in vitro antioxidant activities of Malaysian Gracilaria manilaensis Yamamoto & Trono. J Appl Phycol. 2018;30:3253-60.   DOI
28 Schmidt K, Gunther W, Stoyanova S, Schubert B, Li Z, Hamburger M, et al. Militarinone A, a neurotrophic pyridone alkaloid from Paecilomyces militaris. Org Lett. 2002;4:197-9.   DOI
29 Schroder P, Forster T, Kleine S, Becker C, Richters A, Ziegler S, et al. Neuritogenic militarinone-inspired 4-hydroxypyridones target the stress pathway kinase MAP4K4. Angew Chem Int Ed Engl. 2015;54:12398-403.   DOI
30 Senevirathne M, Ahn CB, Je JY. Enzymatic extracts from edible red algae, Porphyra tenera, and their antioxidant, anti-acetylcholinesterase, and anti-inflammatory activities. Food Sci Biotechnol. 2010;19:1551-7.   DOI
31 Suzuki J, Iwai M, Mogi M, Oshita A, Yoshii T, Higaki J, et al. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol. 2006;26:917-21.   DOI
32 Syad AN, Rajamohamed BS, Shunmugaiah KP, Kasi PD. Neuroprotective effect of the marine macroalga Gelidiella acerosa: identification of active compounds through bioactivity-guided fractionation. Pharm Biol. 2016;54:2073-81.   DOI
33 Api AM, Belsito D, Bhatia S, Bruze M, Calow P, Dagli ML, et al. RIFM fragrance ingredient safety assessment, (2E,6Z)-nona-2,6-dien-1-ol, CAS registry number 28069-72-9. Food Chem Toxicol. 2015;84:S57-65.   DOI
34 Api AM, Belsito D, Botelho D, Bruze M, Burton GA Jr, Buschmann J, et al. RIFM fragrance ingredient safety assessment,(E,Z)-2,6-nonadien-1-ol acetate, CAS registry number 68555-65-7. Food Chem Toxicol. 2019;127:S216-23.   DOI
35 Bayorh M, Rollins-Hairston A, Adiyiah J, Lyn D, Eatman D. Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase. J Renin Angiotensin Aldosterone Syst. 2012;13:353-9.   DOI
36 Alzheimer's Association Report. 2021 Alzheimer's disease facts and figures. J Alzheimer Dement. 2021;17:327-406.   DOI
37 An ZY, Yan YY, Peng D, Ou TM, Tan JH, Huang SL, et al. Synthesis and evaluation of graveoline and graveolinine derivatives with potent anti-angiogenesis activities. Eur J Med Chem. 2010; 45:3895-903.   DOI
38 Cao CY, Zhang CC, Shi XW, Li D, Cao W, Yin X, et al. Sarcodonin G derivatives exhibit distinctive effects on neurite outgrowth by modulating NGF signaling in PC12 cells. ACS Chem Neurosci. 2018;9:1607-15.   DOI
39 Chen B, Geng J, Gao SX, Yue WW, Liu Q. Eplerenone modulates interleukin-33/sST2 signaling and IL-1β in left ventricular systolic dysfunction after acute myocardial infarction. J Interferon Cytokine Res. 2018;38:137-44.   DOI
40 Cheng Y, Schneider B, Riese U, Schubert B, Li Z, Hamburger M. (+)-N-Deoxymilitarinone A, a neuritogenic pyridone alkaloid from the insect pathogenic fungus Paecilomyces farinosus. J Nat Prod. 2006;69:436-8.   DOI
41 Ng PK, Lin SM, Lim PE, Hurtado AQ, Phang SM, et al. Genetic and morphological analyses of Gracilaria firma and G. changii (Gracilariaceae, Rhodophyta), the commercially important agarophytes in western Pacific. PLOS ONE. 2017;12:1-21.
42 Nitthithanasilp S, Intaraudom C, Boonyuen N, Suvannakad R, Pittayakhajonwut P. Antimicrobial activity of cyathane derivatives from Cyathus subglobisporus BCC44381. Tetrahedron. 2018;74:6907-16.   DOI
43 Okubo H, Inagaki H, Gondo Y, Kamide K, Ikebe K, Masui Y, et al. Association between dietary patterns and cognitive function among 70-year-old Japanese elderly: a cross-sectional analysis of the SONIC study. Nutr J. 2017;16:56.   DOI
44 Pangestuti R, Kim SK. Neuroprotective effects of marine algae. Mar Drugs. 2011;9:803-18.   DOI
45 Tanaka K, Kuba Y, Ina A, Watanabe H, Komatsu K. Prediction of cyclooxygenase inhibitory activity of Curcuma rhizome from chromatograms by multivariate analysis. Chem Pharm Bull. 2008;56:936-40.   DOI
46 Vecchiola A, Fuentes CA, Solar I, Lagos CF, Opazo MC, Munoz-Durango N, et al. Eplerenone implantation improved adipose dysfunction averting RAAS activation and cell division. Front Endocrinol. 2020;11:223.   DOI
47 Syad AN, Shunmugiah KP, Kasi PD. Assessment of anticholinesterase activity of Gelidiella acerosa : implications for its therapeutic potential against Alzheimer's disease. Evid Based Complement Alternat Med. 2012;2012:497242.
48 Suganthy N, Karutha Pandian S, Pandima Devi K. Neuroprotective effect of seaweeds inhabiting South Indian coastal area (Hare Island, Gulf of Mannar Marine Biosphere Reserve): cholinesterase inhibitory effect of Hypnea valentiae and Ulva reticulata. Neurosci Lett. 2010;468:216-9.   DOI
49 Wada T, Ishikawa A, Watanabe E, Nakamura Y, Aruga Y, Hasegawa H, et al. Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance. J Endocrinol. 2017;235:179-91.   DOI
50 Xiao J, Shimada M, Liu W, Hu D, Matsumori A. Anti-inflammatory effects of eplerenone on viral myocarditis. Eur J Heart Fail. 2009;11:349-53.   DOI
51 Yow YY, Lim PE, Phang SM. Assessing the use of mitochondrial cox1 gene and cox2-3 spacer for genetic diversity study of Malaysian Gracilaria changii (Gracilariaceae, Rhodophyta) from Peninsular Malaysia. J Appl Phycol. 2013;25:831-8.   DOI
52 Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11:315-35.   DOI
53 Dong F, Xie W, Strong JA, Zhang JM. Mineralocorticoid receptor blocker eplerenone reduces pain behaviors in vivo and decreases excitability in small-diameter sensory neurons from local inflamed dorsal root ganglia in vitro. Anesthesiology. 2012;117:1102-12.   DOI
54 Endo A, Kuroda M, Tsujita Y. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot. 1976;29:1346-8.   DOI
55 Flath RA, Mon TR, Lorenz G, Whitten J, Mackley JW. Volatile components of Acacia sp. blossoms. J Agric Food Chem. 1983;31:1167-70.   DOI
56 Gutierrez M, Matus MF, Poblete T, Amigo J, Vallejos G, Astudillo L, et al. Isoxazoles: synthesis, evaluation and bioinformatic design as acetylcholinesterase inhibitors. J Pharm Pharmacol. 2013;65:1796-804.   DOI
57 Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer's disease: targeting the cholinergic system. Curr Neuropharmacol. 2016;14:101-15.   DOI
58 Hsiao JW, Chen LC, Lin CL, Chang TH, Chen CL, Sung PJ, et al. A new sesquiterpenoid and bioactive constituents of Curcuma zedoaria. Chem Nat Compd. 2020;56:1076-80.   DOI
59 Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci. 2017;24:47.   DOI
60 Jonca J, Zuk M, Wasag B, Janaszak-Jasiecka A, Lewandowski K, Wielgomas B, et al. New insights into butyrylcholinesterase activity assay : serum dilution factor as a crucial parameter. PLOS ONE. 2015;10:e0139480.   DOI
61 Kannan RRR, Aderogba MA, Ndhlala AR, Stirk WA, Van Staden J. Acetylcholinesterase inhibitory activity of phlorotannins isolated from the brown alga, Ecklonia maxima (Osbeck) Papenfuss. Food Res Int. 2013;54:1250-4.   DOI
62 Kemp TR, Knavel DE, Stoltz LP. Identification of some volatile compounds from cucumber. J Agric Food Chem. 1974;22:717-8.   DOI
63 Marcotullio MC, Pagiott R, Maltese F, Obara Y, Hoshino T, Nakahata N, et al. Neurite outgrowth activity of cyathane diterpenes from Sarcodon cyrneus, cyrneines A and B. Planta Med. 2006;72:819-23.   DOI
64 Kihara T, Shimohama S. Alzheimer's disease and acetylcholine receptors. Acta Neurobiol Exp. 2004;64:99-105.
65 Kuenzi P, Kiefer S, Koryakina A, Hamburger M. Promotion of cell death or neurite outgrowth in PC-12 and N2a cells by the fungal alkaloid militarinone A depends on basal expression of p53. Apoptosis. 2008;13:364-76.   DOI
66 Labuzek K, Liber S, Buldak L, Krupej-Kedzierska J, Machnik G, Bobrzyk M, et al. Eplerenone mimics features of the alternative activation in macrophages obtained from patients with heart failure and healthy volunteers. Eur J Pharmacol. 2014;726:96-108.   DOI
67 Lo JY, Kamarudin MNA, Hamdi OAA, Awang K, Kadir HA. Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells. Food Funct. 2015;6:3550-9.   DOI