Sains Malaysiana 47(10)(2018):
2337–2347
http://dx.doi.org/10.17576/jsm-2018-4710-10
Neuroprotective Effects of Ethyl Acetate Extract
of Zingiber zerumbet (L.) Smith against Oxidative Stress on Paraquat-Induced
Parkinsonism in Rats
(Kesan Neurolindungi Ekstrak Etil Asetat Zingiber
zerumbet (L.)
Smith terhadap Tekanan Oksidatif pada Tikus Parkinsonisme Aruhan Parakuat)
FARAH
WAHIDA
IBRAHIM,
UMI
NORAASHIKIN
ZAINUDIN,
MAZLYZAM
ABDUL
LATIF
& ASMAH HAMID*
Biomedical Science Programme, Center for
Health & Applied Sciences, Faculty of Health Sciences, Universiti
Kebangsaan Malaysia, Jalan
Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia
Received: 14 March 2018/Accepted: 5 June 2018
ABSTRACT
Zingiber zerumbet has been traditionally used as an anti-inflammation
and antioxidant agent. The present study investigates the neuroprotective
effects of ethyl acetate extract of Z. zerumbet against
oxidative stress on paraquat (PQ)-induced Parkinsonism in rats.
Forty male Sprague-Dawley rats were divided into five groups:
Negative control (normal saline), positive control (N-acetylcysteine,
NAC 20
mg/kg + PQ 10 mg/kg), PQ only, 200 mg/kg Z. zerumbet
+ PQ and 400 mg/kg Z. zerumbet + PQ.
The extract was given orally for 19 consecutive days and PQ was
administered intraperitoneally on day 8-12th of the treatment
regime. Both serum and fresh brains containing substantia nigra
(SN)
region were taken for biochemical and histological analysis. Administration
of both 200 and 400 mg/kg ethyl acetate Z.
zerumbet extracts to the PQ-treated groups have
resulted in: Decreased levels of MDA and PC in
the SN homogenates; and increased SOD,
GPx; and CAT activities in the SN
and serum. Overall, ethyl acetate extract of Z.
zerumbet reduced oxidative stress in the SN of PQ-induced neuronal damages, therefore,
has the potential to be developed as a preventive agent for neurodegenerative
disorders caused by environmental toxins.
Keywords: Antioxidant;
oxidative stress; paraquat; Parkinson’s
disease; Zingiber zerumbet
ABSTRAK
Zingiber zerumbet
telah digunakan
secara tradisi
sebagai agen anti-keradangan dan antioksidan. Kajian ini dijalankan untuk mengkaji kesan neurolindungi ekstrak etil asetat
Z. zerumbet terhadap
tekanan oksidatif
dalam tikus Parkinsonisme
aruhan parakuat
(PQ).
Empat puluh
tikus Sprague-Dawley jantan dibahagikan kepada lima kumpulan: Kawalan negatif (salin normal), kawalan positif (N-asetilcysteine, NAC 20 mg/kg + PQ 10
mg/kg), PQ sahaja, 200 mg/kg Z. zerumbet + PQ dan
400 mg/kg Z. zerumbet + PQ. Ekstrak diberikan
secara oral gavaj
selama 19 hari berturut-turut dan PQ
diberikan secara intraperitoneal
pada hari ke-8 sehingga ke-12 rejim rawatan. Kedua-dua sampel serum dan
tisu otak
pada bahagian substantia nigra (SN) diambil
untuk analisis biokimia dan histologi.
Pemberian ekstrak
etil asetat Z. zerumbet pada kedua-dua dos 200
dan 400 mg/kg kepada kumpulan yang dirawat PQ
telah: Menurunkan tahap MDA dan PC
dalam homogenat SN;
meningkatkan aktiviti SOD,
GPx, dan CAT dalam SN dan serum;
serta meningkatkan
aras glutation
terturun (GSH) dalam
SN.
Secara
keseluruhannya, ekstrak etil asetat Z. zerumbet didapati
dapat mengurangkan
tekanan oksidatif pada kawasan SN di
otak tikus
yang diaruh kerosakan neuron oleh PQ. Seterusnya, berpotensi
untuk dibangunkan
sebagai agen pencegah
gangguan penyakit
neurodegeneratif yang disebabkan
oleh pendedahan terhadap toksin dari alam sekitar.
Kata kunci: Antioksidan;
parakuat; penyakit
Parkinson; tekanan oksidatif;
Zingiber zerumbet
REFERENCES
Abdelwahab, S.I., Abdul, A.B., Zain, Z.N. & Hadi,
A.H. 2012. Zerumbone inhibits
interleukin-6 and induces apoptosis and cell cycle arrest in ovarian
and cervical cancer cells. International Immunopharmacology
12: 594-602.
Abdelwahab, S.I., Abdul, A.B., Mohan,
S., Taha, M.M., Syam,
S., Ibrahim, M.Y. & Mariod, A.A.
2011. Zerumbone induces apoptosis in t-acute lymphoblastic leukemia
cells. Leukemia Research 35: 268-271.
Abdul, A.B.H., Al-Zubairi, A.S., Tailan, N.D., Wahab, S.I.A., Zain,
Z.N.M., Ruslay, S. & Syam,
M.M. 2008. Anticancer activity of natural compound
(zerumbone) extracts from Zingiber
zerumbet in human hela cervical
cancer cells. Journal of Pharmacology 4: 160-168.
Abdul Hamid, Z., Budin, S.B., Wen Jie, N., Hamid, A., Husain, K. & Mohamed, J. 2012. Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract
against paracetamol-induced nephrotoxicity and oxidative stress
in rats. Journal of Zhejiang University-Science B (Biomedicine
& Biotechnology) 13(3): 176-185.
Aebi, H. 1984. Catalase in vitro. Methods Enzymol. 105:
121-126.
Batubara, L., Suparto, I.H., Sadiah, S., Matsuoka, R. & Mitsunaga,
T. 2013. Effect of Zingiber
zerumbet essential oil and Zerumbone
inhalation on body weight of sprague dawley
rat. Pakistan Journal of Biological Sciences 16: 1028-1033.
Betteridge, D.J. 2000. What
is oxidative stress? Metabolism 49(2 suppl
1): 3-8.
Beyer,
W.F. & Fridovich, I. 1987. Assaying for superoxide dismutase
activity: Some large consequences of minor changes in conditions.
Anal Biochem. 161(2): 559-566.
Bhuiyan, M.N.I., Chowdhury, J.U. & Begum, J. 2009. Chemical investigation of the leaf and rhizome
essential oils of Zingiber
zerumbet (L.) Smith from Bangladesh.
Bangladesh Journal of Pharmacology 4: 9-12.
Blanco-Ayala, T., Andérica-Romero, A.C.
& Pedraza-Chaverri, J. 2014. New insights into antioxidant strategies against
paraquat toxicity. Free Radical
Research 48(6): 623-640.
Blesa, J., Phani,
S., Jackson-Lewis, V. & Przedborski,
S. 2012. Classic and new animal models of Parkinson’s disease.
Journal of Biomedicine and Biotechnology 2012: 1-10.
Bradford, M.M. 1976. A rapid
and sensitive method for the quantitation of microgram quantities
of protein utilizing the principle of protein-dye binding.
Anal Biochem. 72: 248-254.
Brooks, A.I., Chadwick, C.A.,
Gelbard, H.A., Cory-Slechta, D.A. & Federoff, H.J. 1999. Paraquat
elicited neurobehavioral syndrome caused by dopaminergic neuron
loss. Brain Res. 823(1-2): 1-10.
Budin, S.B., Rahmat Sam, M.F., Hamid, A. &
Ghazali, A.R. 2013. Evaluation of the antiradical and antioxidant
potential of Zingiber zerumbet
rhizome. The Open Conference Proccedings
Journal 4: 157.
Cha, E.S., Khang, Y.H. & Lee, W.J. 2014. Mortality from
and incidence of pesticide poisoning in South Korea: Findings
from national death and health utilization data between 2006 and
2010. PLoS One 9(4): e95299.
Chinta, J.S., Kumar, M.J., Hsu, M., Rajagopalan,
S., Kaur, D., Rane, A., G. Nicholls,
D., Choi, J. & Andersen, J.K 2007. Inducible alterations of glutathione
levels in adult dopaminergic midbrain neurons result in nigrostriatal
degeneration. The Journal of Neuroscience 27(51): 13997-
14006.
Coward, D.M., Doggett, N.S.
& Sayers, A.C. 1977. The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine
hydrochloride (LON-954) a new tremorogenic agent. Arzneimittelforschung
27(12): 2326-2332.
Danielson, S.R. & Anderson, J.K. 2008. Oxidative and nitrative
protein modifications in Parkinson’s disease. Free Radical
Biology & Medicine 44: 1787-1794.
Dalle-Donne, I., Giustarini, D., Colombo, R.,
Rossi, R. & Milzani, A. 2003 Protein
carbonylation in human diseases. Trends in Molecular Medicine 9(4): 169-176.
Essa, M.M., Vijayan, R.K., Castellano-Gonzalez,
G., Memon, M.A., Braidy, N. & Guillemin, G.J. 2012. Neuroprotective effects of natural products against Alzheimer’s
disease. Neurochemical Research 37(9): 1829-1842.
Giasson, B.I., Ischiropoulos, H., Lee, V.M.Y.
& Trojanowski, J.Q. 2002. The relationship between oxidative/nitrative
stress and pathological inclusions in Alzheimer’s and Parkinson’s
Disease. Free Radical Biology & Medicine 32:
1264-1275.
Goldman, S.M., Kamel, F., Ross, G.W., Bhudhikanok, G.S., Hoppin, J.A.,
Korell, M., Marras, C., Meng, C., Umbach, D.M., Kasten, M., Chade, A.R., Comyns, K., Richards, M.B., Sandler, D.P., Blair, A., Langston,
J.W. & Tanner, C.M. 2012. Genetic modification of the association of paraquat
and Parkinson’s disease. Movement Disorders 27(13):
1652-1658.
Gujral, S.J., Knight, R.T., Farhood, A., Bajt, M.L. & Jaeschke, H. 2002. Mode of cell death after acetominophen
overdose in mice: Apoptosis or oncotic necrosis? Toxicological
Sciences 67: 322-328.
Habsah, M., Amran, M., Mackeen,
M.M., Lajis, N.H. & Kikuzaki,
H. 2000. Screening of Zingiberaceae
extracts for antimicrobial and antioxidant activities. Journal
of Ethnopharmacol. 72:
403-410.
Hamid, A., Budin, S.B., Mohamed, R.A.P.,
Manaf, N.A., Yuhana,
N.Y., Husain, K., Hamid, Z.A. & Mohamed, J. 2011. Role of
oxidative stress in the protective effects of Zingiber
zerumbet Smith ethyl-acetate extract against paracetamol-induced
hepatotoxicity in sprague-dawley rat. Australian Journal of Basic and Applied
Sciences 5(8): 1519-1525.
Hamid, A., Ibrahim, F.W., Teoh, H.M., Nasrom,
M.N., Eusoff, N., Husain, K. & Abdul
Latif, M. 2018. Zingiber zerumbet
L. (Smith) extract alleviates the ethanol-induced brain damage
via its antioxidant activity. BMC Complementary and Alternative
Medicine 18(1): 101.
Hirsch, L., Jette, N., Frolkis, A., Steeves, T. & Pringsheim, T. 2016. The
incidence of Parkinson’s Disease: A systematic
review and meta-analysis. Neuroepidemiology
46(4): 292- 300.
Huang, C.L., Chao, C.C., Lee, Y.C., Lu, M.K., Cheng, J.J., Yang,
Y.C., Wang, V.C., Chang, W.C. & Huang, N.K. 2016. Paraquat induces cell death through impairing
mitochondrial membrane permeability. Molecular Neurobiolology
53(4): 2169-2188.
Ibrahim, M.Y., Abdul, A.B.H., Ibrahim, T.A.T., Wahab,
S.I.A., Elhassan, M.M. & Mohan, S. 2010. Attenuation
of cisplastin-induced nephrotoxicity in rats using zerumbone. African Journal of Biotechnology 9(28):
4434-4441.
Kadiiska, M.B., Gladen,
B.C., Baird, D.D., Germolec, D., Graham,
L.B., Parker, C.E., Nyska, A., Wachsman,
J.T., Ames, B.N., Basu, S., Brot,
N., FitzGerald, G.A., Floyd, R.A., Goerge,
M., Heinecke, J.W., Hatch, G.E., Hensley, K., Lawson, J.A., Marnett, L.J., Morrow, J.D., Murray, D.M., Plataras, J., Roberts II, L.J., Rokach,
J., Shigenaga, M.K., Sohal,
R.S., Sun, J., Tice, R.R., Van Thiel, D.H., Wellner,
D., Walter, P.B., Tomer, K.B., Mason,
R.P. & Barrett, J.C 2005. Biomarkers of oxidative stress study
II. Are oxidation products of lipids, proteins, and DNA markers
of CCl4 poisoning? Free Radical Biology & Medicine 38(2005):
698-710.
Kaplowitz, N. 2000. Mechanism
of liver cell injury. Journal of Hepatology 32(S1):
39-47.
Lascano, R., Muñoz, N., Robert, G.N., Rodriguez, M., Melchiorre,
M., Trippi, V. & Querol,
G. 2012. Paraquat: An
oxidative stress inducer. Herbicides - Properties,
Synthesis and Control of Weeds. Rijeka, Croatia: InTech.
pp. 135-148.
Ledwozyw, A., Michalak, J., Stepien, A.
& Kadziolka, A. 1986. The relationship between plasma triglycerides,
cholesterol, total lipids and lipid peroxidation products during
human atherosclerosis. Clin Chim Acta. 155(3): 275-283.
Levine, R.L., Garland, D., Oliver, C.N.,
Amici, A., Climent, I., Lenz, A.G., Ahn, B.W., Shaltiel, S. &
Stadtman, E.R. 1990. Determination of carbonyl content in oxidatively
modified protein. Methods Enzymol. 186: 464-478.
Lewis, A.P. & Cookson, R.M. 2012. Gene expression in the Parkinson’s Disease
brain. Brain Research Bulletin 88(2012): 302-312.
McCollum, M., Ma, Z., Cohen, E., Leon, R., Tao, R., Wu, J.Y., Maharaj, D. & Wei, J. 2010. Post-MPTP treatment with granulocyte colony-stimulating factor improves
nigrostriatal function in the mouse model of parkinson’s disease. Molecular Neurobiology 41:
410-419.
Montine, T., Neely, M., Quinn, J., Beal, M., Markesbery,
W., Roberts, L. & Morrow, J. 2002. Lipid
peroxidation in aging brain and Alzheimer’s
Disease. Free Radical Biology & Medicine 33(5):
620-626.
Nakamura, Y., Yoshida, C., Murakami, A., Ohigashi,
H., Osawa, T. & Uchida, K. 2004. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes.
FEBS Letter 572(1-3): 245-250.
Nikolova, G. 2012. Oxidative stress and Parkinson disease. Trakia
Journal of Sciences 10: 92-100.
Nordberg, J. & Arner, E.S. 2001. Reactive oxygen species, antioxidants, and the
mammalian thioredoxin system.
Free Radical Biology & Medicine 31: 1287-1312.
Ogunro, P.S., Mustapha, A.F., Oshodi, T.T., Adebayo, R.A., Atiba,
A.S., Akande, J.O. & Oke,
O.Z. 2014. Alteration in antioxidants level
and lipid peroxidation of patients with neurodegenerative diseases
{Alzheimer’s disease and Parkinson disease}. International
Journal of Nutrition, Pharmacology, Neurological Diseases 4(3):
146-152.
Perfeito, R., Cunha-Oliveira, T. & Rego, C.A.
2012. Revisiting oxidative
stress and mitochondrial dysfunction in the pathogenesis of Parkinson
disease-resemblance to the effect of amphetamine drugs of abuse.
Free Radical Biology & Medicine 53(9): 1791-1806.
Poljsak, B., Suput, D. & Milisav, I. 2013. Achieving the balance between ROS and antioxidants: When to use the
synthetic antioxidants. Oxidative Medicine and Cellular
Longevity 2013: 956792.
Rao, P.S., Kalva, S., Yerramilli, A. & Mamidi, S.
2011. Free radicals and tissue damage: Role of antioxidants. Free
Radical and Antioxidant 1(4): 2-7.
Ruslay, S., Abas, F., Shaari, K., Zainal, Z.,
Maulidiani, Sirat, H., Israf, D.A. & Lajis, N.H. 2007. Characterization of the components present in the active fractions
of health gingers (Curcuma xanthorrhiza
and Zingiber zerumbet)
by HPLC-DAD-ESIMS. Food Chemistry 104: 1183-1191.
Sanyal, J., Sarkar, B., Banerjee, T.K., Mukherjee, S.C., Ray, B.C. &
Rao, V.R. 2011. Peripheral markers for oxidative
stress in Parkinson’s Disease patients
of Eastern India. Neurochemical Journal 5(2): 146-149.
Seet, R.C.S., Lee, C.Y.J., Lim,
E.C.H., Tan, J.J.H., Quek, A.M.L., Chong,
W.L., Looi, W.F., Huang, S.H., Wang, H., Chan, Y.H. & Halliwel, B. 2010. Oxidative damage in Parkinson Disease:
Measurement using accurate biomarkers. Free Radical Biology
& Medicine 48: 560-566.
Shafique, H., Blagrove, A., Chung, A. & Logendrarajah, R. 2011. Causes
of Parkinson’s Disease: Literature review.
Journal of Parkinsonism & Restless Legs Syndrome 1(1):
7-9.
Shimizu, K., Matsubara, K., Ohtaki, K.,
Fujimaru, S., Siato, O. & Shiono,
H. 2003. Paraquat
induces long-lasting dopamine overflow through the excitotoxic
pathway in the striatum of freely moving rats. Brain Research
976(2): 243-252.
Somayajulu-Nitu, M., Sandhu, J.K.,
Cohen, J., Sikorska, M., Sridhar, T.,
Matei, A., Borowy-Borowski, H. &
Pandey, S. 2009. Paraquat induces oxidative
stress, neuronal loss in substantia nigra
region and Parkinsonism in adult rats: Neuroprotection and amelioration
of symptoms by water-soluble formulation of Coenzyme Q10. BMC
Neuroscience 10: 1-12.
Somchit, M.N., Shukriyah, M.H.N., Bustamam, A.A. & Zuraini, A.
2005. Anti pyretic and analgesic activity of Zingiber
zerumbet. International Journal of Pharmacology
1: 277-280.
Somchit, M.N., Mak, J.H., Ahmad Bustamam, A., Zuraini, A., Arifah, A.K., Adam, Y. & Zakaria, Z.A. 2012. Zerumbone isolated from Zingiber zerumbet inhibits inflammation and
pain in rats. Journal of Medicinal Plants Research 6(2):
177-180.
Thannan, R., Oikawa, S., Hiraku, Y., Ohnishi, S., Ma, N., Pinlaor,
S., Yangvanit, P., Kawanishi,
S. & Murata, M. 2015. Oxidative stress and
its significant roles in neurodegenerative diseases and cancer.
International Journal of Molecular Sciences 16: 193-217.
Wakabayashi, K., Tanji, K., Mori, F. &
Takahasi, H. 2007. The Lewy body in Parkinson’s disease: Molecules implicated in the
formation and degradation of alpha-synuclein
aggregates. Neuropathology 27(5): 494-506.
Wesseling, C., van Wendel, de Joode B., Ruepert, C., León,
C., Monge, P., Hermosillo, H. & Partanen, T.J. 2001. Paraquat
in developing countries. Int. J. Occup. Environ. Health. 7(4):
275-286.
Yang, W. & Tiffany-Castiglioni, E. 2005. The bipyridyl herbicide paraquat produces oxidative stress-mediated toxicity in human
neuroblastoma SH-SY5Y cells: Relevance to the dopaminergic pathogenesis.
Journal of Toxicology and Environmental Health Part A
68(22): 1939-1961.
Yob, N.J., Jofrry, S.M., Affandi, M.M., Teh, L.K., Salleh, M.Z. & Zakaria, Z.A.
2011. Zingiber zerumbet (L.) Smith: A review of its ethnomedicinal, chemical, and pharmacological uses. Evidence-Based
Complementary and Alternative Medicine: eCAM
2011: 543216.
Yokoyama, H., Kuroiwa, H., Yano, R. &
Araki, T. 2008. Targeting
reactive oxygen species, reactive nitrogen species and inflammation
in MPTP neurotoxicity and Parkinson’s disease. Neurolological
Sciencs 29: 293-301.
*Corresponding author; email: asmah0901@ukm.edu.my