Sains Malaysiana 47(12)(2018): 3009–3015
http://dx.doi.org/10.17576/jsm-2018-4712-10
Mucuna pruriens Seed Extract Promotes Neurite Outgrowth
via Ten-4 Dependent and Independent Mechanisms in Neuro2a Cells
(Ekstrak Biji Mucuna pruriens Menggalakkan
Pertumbuhan Neurit melalui Mekanisme
Pergantungan Ten-4 dan Mekanisme Bebas Ten-4
dalam Sel Neuro2a)
SUTIN WANSAWAT1, MANI
IYER PRASANTH2, CIRO ISIDORO3 & TEWIN TENCOMNAO1,2*
1Clinical Biochemistry
and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied
Health Sciences, Chulalongkorn University, 10330 Bangkok, Thailand
2Age-related Inflammation
and Degeneration Research Unit, Department of Clinical Chemistry, Faculty of
Allied Health Sciences, Chulalongkorn University, 10330 Bangkok, Thailand
3Laboratory of Molecular
Pathology, Department of Health Sciences, Università del
Piemonte Orientale 'A. Avogadro', Novara, Italy
Diserahkan: 30 Mei 2018/Diterima:
18 September 2018
ABSTRACT
Neurological diseases are one of the
serious health hazards faced by mankind for decades. Neurite outgrowth
is a key factor responsible for proper neuronal development. Any
misplacement in the process could lead to neurological diseases
like Alzheimer's and Parkinson's. Treatment with the available
synthetic drugs imparts many difficulties to the patients due
to the side effects. Compounds from natural sources can be considered
as an effective replacement for this. Mucuna pruriens,
used in traditional ayurvedic medicine, contains L-3,4-dihydroxy
phenylalanine (L-DOPA) in its seeds, which possesses
medicinal effects against neurological diseases. In this regard,
seed extracts of M. pruriens originated from Thailand and
India, were analyzed for their neuroprotective effects in Neuro2a
cells. Hexane, ethyl acetate and ethanol extracts were found to
be non-toxic to the viability of the cells. Ethanol extracts of
M. pruriens of Thai origin (MTE),
hexane extracts of M. pruriens of Indian origin (MIH)
and ethyl acetate extracts of M. pruriens of Indian origin
(MIEA)
were able to induce neurite outgrowth in Neuro2a cells. Interestingly,
both MTE
and MIH
induced neurite outgrowth dependent on Teneurin-4
(Ten-4) transmembrane protein whereas MIEA did the same independent
of Ten-4, which was confirmed by real time PCR and
gene silencing approach. The present study suggested that M.
pruriens can be used as a potential drug in the treatment of
neurological diseases as it can induce neurite outgrowth by multiple
mechanisms, which will be of great use in the field of medicine.
Keywords: Neurite outgrowth; neuro2a
cells; neurodegenerative diseases; Ten-4
ABSTRAK
Penyakit neurologi adalah salah satu
penyakit serius yang dihadapi oleh manusia selama beberapa dekad.
Pertumbuhan neurit merupakan faktor utama yang bertanggungjawab
untuk perkembangan neuron yang betul. Sebarang kesilapan dalam
proses tersebut boleh membawa kepada penyakit neurologi seperti
Alzheimer dan Parkinson. Rawatan dengan ubatan sintetik sedia
ada memberikan banyak kesulitan kepada pesakit akibat kesan sampingan.
Sebatian daripada sumber semula jadi boleh dianggap sebagai pengganti
berkesan untuk ini. Biji Mucuna pruriens yang digunakan dalam perubatan tradisi ayurveda,
mengandungi L-3,4-dihidroksi fenilalanina (L-DOPA)
yang mempunyai kesan perubatan terhadap penyakit neurologi. Dalam
hal ini, ekstrak biji benih daripada M. pruriens yang berasal
dari Thailand dan India, dianalisis untuk kesan neuroperlindungan
di dalam sel Neuro2a. Ekstrak heksana, etil asetat dan etanol
didapati tidak toksik kepada kebolehidupan sel-sel. Ekstrak etanol
M. pruriens Thailand (MTE),
ekstrak heksana dari M. pruriens India (MIH)
dan ekstrak etil asetat dari M. pruriens India (MIEA)
dapat mendorong pertumbuhan neurit dalam sel Neuro2a. Kedua-dua
MTE dan
MIH
yang menggalakkan pertumbuhan neurit bergantung
kepada protein transmembran Teneurin-4 (Ten-4) manakala MIEA tidak bergantung pada Ten-4.
Ini telah disahkan menggunakan PCR dan pendekatan penyenyapan
gen. Kajian ini menunjukkan bahawa M. pruriens boleh digunakan
sebagai ubat berpotensi dalam merawat penyakit neurologi kerana
ia dapat mendorong pertumbuhan neurit melalui pelbagai mekanisme,
yang dapat digunakan dengan baik dalam bidang perubatan.
Kata
kunci: Penyakit 'neurodegenerative'; pertumbuhan neurit; sel Neuro2a;
Ten-4
RUJUKAN
Brimson,
J.M., Safrany, S.T., Qassam, H. & Tencomnao, T. 2018. Dipentylammonium
binds to the sigma-1 receptor and protects against glutamate toxicity,
attenuates dopamine toxicity and potentiates neurite outgrowth in various
cultured cell lines. Neurotox. Res. 34(2): 263-272.
Chen, G.,
Bower, K.A., Xu, M., Ding, M., Shi, X., Ke, Z.J. & Luo, J. 2009.
Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth:
Role of glycogen synthase kinase 3 Beta. Neurotox. Res. 15(4): 321-331.
Gundimeda,
U., McNeill, T.H., Schiffman, J.E., Hinton, D.R. & Gopalakrishna, R. 2010.
Green tea polyphenols potentiate the action of nerve growth factor to induce
neuritogenesis: Possible role of reactive oxygen species. J. Neurosci. Res.
88(16): 3644-3655.
Jesky, R.
& Chen, H. 2016. The neuritogenic and neuroprotective potential of
senegenin against Aβ-induced neurotoxicity in PC 12 cells. BMC
Complement. Altern. Med. 16: 26.
Lampariello,
L.R., Cortelazzo, A., Guerranti, R., Sticozzi, C. & Valacchi, G. 2012. The
magic velvet bean of Mucuna pruriens. J. Tradit. Complement. Med.
2(4): 331-339.
Ma, Y.Z.,
Ning, N., He, W.B., Li, J.W., Hu, J.F., Chu, S.F. & Chen, N.H. 2013.
Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling
pathway. Acta Pharmacol. Sin. 34(12): 1499-1507.
Mena, M.A., Davila, V.,
Bogaluvsky, J. & Sulzer, D.A. 1998. Synergistic neurotrophic response to
l-dihydroxyphenylalanine and nerve growth factor. Mol. Pharmacol. 54(4):
678-686.
More, S.V., Koppula, S., Kim, I.S., Kumar, H., Kim, B.W.
& Choi, D.K. 2012. The role of bioactive compounds on the promotion of
neurite outgrowth. Molecules 17(6): 6728-6753.
Phan, C.W., David, P.,
Naidu, M., Wong, K.H. & Sabaratnam, V. 2013. Neurite outgrowth stimulatory
effects of culinary-medicinal mushrooms and their toxicity assessment using
differentiating Neuro-2a and embryonic fibroblast BALB/3T3. BMC Complement.
Altern. Med. 13: 261.
Phan, C.W., David, P.,
Wong, K.H., Naidu, M. & Sabaratnam, V. 2015. Uridine from Pleurotus
giganteus and its neurite outgrowth stimulatory effects with underlying
mechanism. PLoS One 10(11): e0143004.
Pulikkalpura, H., Kurup,
R., Mathew, P.J. & Baby, S. 2015. Levodopa in Mucuna pruriens and
its degradation. Sci. Rep. 5: 11078.
Raina, A.P. &
Khatri, R. 2011. Quantitative determination of L-DOPA in seeds of Mucuna
pruriens germplasm by high performance thin layer chromatography. Indian
J. Pharm. Sci. 73(4): 459-462.
Riaz, M., Shahid, M.,
Jamil, A. & Saqib, M. 2017. In vitro antioxidant potential of
selected aphrodisiac medicinal plants. J. Biol. Regul. Homeost. Agents 31(2):
419-424.
Sarina, Y., Nakano, O.,
Hashimoto, T., Kimura, K., Asakawa, Y., Zhong, M., Narimatsu, S. & Gohda,
E. 2013. Induction of neurite outgrowth in PC12 cells by artemisinin through
activation of ERK and p38 MAPK signaling pathways. Brain Res. 1490:
61-71.
Suzuki, N., Numakawa,
T., Chou, J., de Vega, S., Mizuniwa, C., Sekimoto, K., Adachi, N., Kunugi, H.,
Arikawa-Hirasawa, E., Yamada, Y. & Akazawa, C. 2014. Teneurin-4 promotes
cellular protrusion formation and neurite outgrowth through focal adhesion
kinase signaling. FASEB J. 28(3): 1386-1397.
Suzuki, N., Fukushi, M.,
Kosaki, K., Doyle, A.D., de Vega, S., Yoshizaki, K., Akazawa, C.,
Arikawa-Hirasawa, E. & Yamada, Y. 2012. Teneurin-4 is a novel regulator of
oligodendrocyte differentiation and myelination of small-diameter axons in the
CNS. J. Neurosci. 32(34): 11586-11599.
Wang, Y.P., Wang, Z.F.,
Zhang, Y.C., Tian, Q. & Wang, J.Z. 2004. Effect of amyloid peptides on
serum withdrawal-induced cell differentiation and cell viability. Cell Res.
14(6): 467-472.
Zhang, Z., Cai, L.,
Zhou, X., Su, C., Xiao, F., Gao, Q. & Luo, H. 2015. Methyl
3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite
outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway. Neuroreport 26(6): 367-373.
*Pengarang untuk surat-menyurat; email: tewin.t@chula.ac.th