Antioxidative, Anticholinesterase and Anti-Neuroinflammatory Properties of Malaysian Brown and Green Seaweeds

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.





References:
[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.