Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 30458
Antioxidative, Anticholinesterase and Anti-Neuroinflammatory Properties of Malaysian Brown and Green Seaweeds

Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan


Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several proinflammatory cytokines, nitric oxide (NO) and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anticoagulation, antimicrobial, antioxidative, anticancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. These seaweeds significantly exhibited potent DPPH and moderate superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.157±0.004mg/ml and 0.849±0.02mg/ml for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.386±0.01mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 50% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118- 0.287 mg/ml.

Keywords: neuroinflammation, anticholinesterase, seaweeds, antioxidative

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 2227


[1] Vladimir-Knezevic S, Blazekovic B, Kindl M, Vladic J, Lower-Nedza AD, Brantner AH. Acetylcholinesterase inhibitory, antioxidant and phytochemical properties of selected medicinal plants of the Lamiaceae family. Molecules 2014;19(1):767-782.
[2] Zhao Y, Dou J, Wu T, Aisa HA. Investigating the antioxidant and acetylcholinesterase inhibition activities of Gossypium herbaceam. Molecules 2013; 18(1):951-962.
[3] Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, et al. Antioxidant approaches for the treatment of Alzheimer's disease. Expert Rev Neurother 2010;10(7):1201-1208.
[4] Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001;60(8):759-767.
[5] Rubio-Perez JM, and Morillas Ruiz JM. A Review: Inflammatory process in Alzheimer's Disease, role of cytokines. Scientific World Journal 2012; 2012(756357).
[6] Schlachetzki JC, Hull M. Microglial activation in Alzheimer's disease. Curr Alzheimer Res 2009;6(6):554-563.
[7] Schwab C, Klegeris A, McGeer PL. Inflammation in transgenic mouse models of neurodegenerative disorders. Biochem Biophys Acta 2010;1802(10):889-902.
[8] Chanda S, Dave R, Kaneria M, Nagani K. Seaweeds: A novel, untapped source of drugs from sea to combat Infectious diseases. Current Research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology 2010;1:473-480.
[9] Molyneux PI. The use of stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J Sci Technol 2004;26(2):211-219.
[10] Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999;26(9-10):1231-1237.
[11] Hsia-Yin L, Cheng-Chun C. Antioxidative activities of water-soluble disaccharide chitosan derivatives. Food Res. Int. 2004;37(9):883–889.
[12] Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961 Jul; 7:88-95
[13] Li J, O W, Li W, Jiang Z, Ghanbari HA. Oxidative stress and neurodegenerative disorders. Int. J. Mol. Sci. 2013;14(12):24438-24475.
[14] Ghasemzadeh A, Jaafar HZE, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules 2010;15(6):4324-4333.
[15] Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. J. Am. Heart ISO 2004;25:29-38.
[16] Bin-Gui W, Wei-Wei Z, Xiao-Juan D, Xiao-Ming L. In vitro antioxidative activities of extract and semi-purified fractions of the marine red alga, Rhodomela confervoides(Rhodomelaceae). Food Chem 2009;113(4):1101–1105.
[17] Yan X, Chuda Y, Suzuki M, Nagata T. Fucoxanthin as the major antioxidant in Hizikia fusiformis, a common edible seaweed. Biosci. Biotechnol. Biochem. 1999; 63:605–607.
[18] Budhiyanti SA, Raharjon S, Marseno DW. Antioxidant activity of brown algae Sargassum species extract from the coastline of Java Island. American J. Agricul. Bio. Sci. 2012; 7(3):337-346.
[19] Sheikh TZB, Yong CL, Lian MS. In vitro antioxidant activity of the hexane and methanolic extracts of Sargassum baccularia and Cladophora patentiramea. J. Appl. Sci. 2009; 9(13):2490-2493.
[20] Bambang BS, Kumalaningsih S, Susinggih W. Polyphenol content and antioxidant activities of crude extract from brown algae by various solvents. J. Life Sci. Biomed. 2013;3(6):439-443.
[21] Foon TS, Ai Ai L, Kuppusamy P, M.Yusoff M, Govindan N. Studies on in-vitro antioxidant activity of marine edible seaweeds from the east coastal region of Peninsular Malaysia using different extraction methods. J. Coast. Life Med. 2013;1(3):193-198.
[22] Palanisamy SK, Sellappa S. Evaluation of antioxidant activity and total phenolic content of Padina boergesenii from Gulf of Mannar. Academic Journal 2012;4(12):635.
[23] Nguyen VT, Ueng J, Tsai G. Proximate composition, total phenolic content, and antioxidant activity of seagrape (Caulerpa lentillifera). J. Food Sci. 2011;76(7):950-958.
[24] Zhongrui L, Bin W, Qihong Z, Youle Q, Huanzhi X, Guoqiang L. Preparation and antioxidant property of extract and semipurified fractions of Caulerpa racemosa. J. Appl. Phycol. 2012;24:1527-1536.
[25] Sanaa MM. Antioxidant and antibiotic activities of some seaweeds (Egyptian isolates). Int J Agri Biol 2007;9(2):220-225.
[26] Frankel E, Meyer A. The problems of using one‐dimensional methods to evaluate multifunctional food and biological antioxidants. J. Sci. Food Agri. 2000;80(13):1925 - 1941.
[27] Movahedinia A, Heydari M. Antioxidant activity and total phenolic content in two alga species from the Persian Gulf in Bushehr province, Iran. Int. J. Sci. Res. 2014;3(5).
[28] Yangthong M, Hutadilok-Towatana N, Phromkunthong W. Antioxidant activities of four edible seaweeds from the southern coast of Thailand. Plant Foods Hum Nutr 2009;64(3):218-223.
[29] Cavas L, Yurdakoc K. A comparative study: Assessment of the antioxidant system in the invasive green alga Caulerpa racemosa and some macrophytes from the Mediterranean. J. Exp. Mar. Biol. Ecol.2005;321(1):35.
[30] Das A, Shanker G, Nath C, Pal R, Singh S, Singh H. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol. Biochem. Behav. 2002;73(4):893-900.
[31] Yu Q, Holloway HW, Utsuki T, Brossi A, Greig NH. Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease. J. Med. Chem. 1999;42(10):1855-1861.
[32] Greig NH, Lahiri DK, Sambamurti K. Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int. Psychogeriatr. 2002;14(1):77-91.
[33] Giacobini E. Drugs that target cholinesterase. Cognitive Enhancing Drugs 2004:11-36.
[34] Lane RM, Kivipelto M, Greig NH. Acetylcholinesterase and its inhibition in Alzheimer disease 2004;27(3):141-149.
[35] Ghannadi A, Plubrukarn A, Zandi K, Sartavi K, Yegdaneh A. Screening for antimalarial and acetylcholinesterase inhibitory activities of some Iranian seaweeds. Res. Pharm. Sci. 2013;8(2):113-118.
[36] Jung HW, Yoon CH, Park KM, Han HS, Park YK. Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. Food Chem.Toxicol. 2009;47(6):1190- 1197.
[37] Murphy S. Production of nitric oxide by glial cells: regulation and potential roles in the CNS. Glia 2000 1;29(1):1-13.
[38] Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004;63(9):901- 910.
[39] Giovannini MG, Scali C, Prosperi C, Bellucci A, Pepeu G, Casamenti F. Experimental brain inflammation and neurodegeneration as model of Alzheimer's disease: protective effects of selective COX-2 inhibitors. Int J Immunopathol Pharmacol 2003;16(2 Suppl):31-40.
[40] Song JD, Lee SK, Kim KM, Kim JW, Kim JM, Yoo YH, et al. Redox factor-1 mediates NF-kappaB nuclear translocation for LPS-induced iNOS expression in murine macrophage cell line RAW 264.7. Immunology 2008;124(1):58-67.
[41] Marks-Konczalik J, Chu SC, Moss J. Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor kappaB-binding sites. J. Biol. Chem. 1998 28;273(35):22201-22208.
[42] Kim M, Kim K, Jeong D, Ahn D. Anti-inflammatory activity of ethanolic extract of Sargassum sagamianum in RAW 264.7 cells. Food Sc. Biotechnol. 2013;22(4):1113-1120.
[43] Weon-Jong Y, Young Min H, Sang-Suk K, Byoung-Sam Y, Ji-Young M, Jong Seok B, et al. Suppression of pro-inflammatory cytokines, iNOS, and COX-2 expression by brown algae Sargassum micracanthum in RAW 264.7 macrophages. EurAsia J BioSci 2009;3:130-143.
[44] Jayasooriya R, Moon D, Choi YH, Yoon CH, Kim GY. Methanol extract of Hydroclathrus clathratus inhibits production of nitric oxide, prostaglandin E2 and tumor necrosis factor-α in lipopolysaccharidestimulated BV2 microglial cells via inhibition of NF-κB activity. Trop. J. Pharm. Res 2011;10(6):723-730.
[45] Jung WK, Ahn YW, Lee SH, Choi YH, Kim SK, Yea SS, et al. Ecklonia cava ethanolic extracts inhibit lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2 microglia via the MAP kinase and NF-kappaB pathways. Food Chem Toxicol 2009 ;47(2):410-417
[46] Lim SJ, Aida WMW, Maskat MY, Mamot S, Ropien J, Mohd DM. Isolation and antioxidant capacity of fucoidan from selected Malaysian seaweeds. Food Hydrocolloids 2014:1-9.
[47] Eluvakkal T, Sivakumar S, Arunkumar K. Fucoidan in some indian brown seaweeds found along the Coast Gulf of Mannar. Int J Bot 2010;6(2).
[48] Park HY, Han MH, Park C, Jin CY, Kim GY, Choi IW. Antiinflammatory effects of fucoidan through inhibition of NF-kappaB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem. Toxicol. 2011;49(8):1745-1752.
[49] Cui YQ, Zhang LJ, Zhang T, Luo DZ, Jia YJ, Guo ZX. Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide-activated primary microglia. Clin. Exp. Pharmacol. Physiol. 2010;37(4):422-428.
[50] Heinrich M, Bork PM, Schmitz ML, Rimpler H, Frei B, Sticher O. Pheophorbide A from Solanum diflorum interferes with NF-kappa B activation. Planta Med 2001;67(2):156-157.
[51] Son Y, Jin S, Kim H, Woo H, Jung H, Choi J. Inhibitory activities of the edible brown alga Laminaria japonica on glucose-mediated protein damage and rat lens aldose reductase. Fisheries Sci 2011;77(6):1069- 1079.
[52] Islam MN, Ishita IJ, Jin SE, Choi RJ, Lee CM, Kim YS, et al. Antiinflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS-stimulated RAW 264.7 macrophage cells. Food Chem Toxicol 2013;55:541-548.