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Sains Malaysiana 52(1)(2023):
http://doi.org/10.17576/jsm-2023-5201-19
Ethanol
Extract of Centella asiatica Improved
Methamphetamine-Induced Neurotoxicity on Mouse Model via Stimulating Superoxide
Dismutase II and microRNA-34A Expression
(Ekstrak
Etanol Centella asiatica Menambahbaik
Keneurotoksikan Teraruh Metamfetamin pada Model Tikus melalui Superoksida
Dismutase II dan Ekspresi Mikro)
NURSYAMILA SHAMSUDDIN1, MAZATULIKHMA MAT ZAIN2,
MOHD ILHAM ADENAN3 &
MOHD SHIHABUDDIN AHMAD NOORDEN1,*
1Faculty of Pharmacy, Universiti Teknologi MARA (UiTM),
Puncak Alam Campus, 42300 Puncak Alam, Selangor Darul Ehsan, Malaysia
2Institute of Science (IOS), Universiti Teknologi MARA
(UiTM), 40000 Shah Alam, Selangor Darul Ehsan, Malaysia
3Atta-ur-Rahman Institute for Natural Product Discovery
(AuRins), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Puncak
Alam, Selangor Darul Ehsan, Malaysia
Received:
20 May 2022/Accepted: 23 August 2022
Abstract
Neurotoxicity
induced by a psychostimulant drug, methamphetamine (METH) is associated with
devastating and persistent neurotoxicity effects on the central nervous system
(CNS). Centella asiatica (CA) is
known as an antioxidant and neuroprotective agent. However, there is a limited
study on natural-derived therapeutic to attenuate neurotoxicity induced by
METH. We aimed to investigate the effects of METH and ethanol extract CA (CAE)
on motor performance of animal model and the expression of manganese superoxide
dismutase II (SOD2) and microRNA-34a (miR-34a) in the brain tissue. Male Sprague-Dawley rats were
administered with METH (50 mg/kg per body weight) twice per day for 4 days, CAE
(300 mg/kg & 500 mg/kg per body weight for 21 days and combination of METH
and CAE for 21 day(s). Weight of rat was measured and motor performance was
evaluated using vertical pole and narrow beam tests. Expression of SOD2 and
miR-34a were measured using Quantitative Real-time Polymerase Chain Reaction
(RT-qPCR). Group III
(300 mg/kg CAE); p<0.001, Group IV (500 mg/kg CAE); p<0.001, Group V
(METH+300 mg/kg CAE); p<0.01 and Group VI (METH+500 mg/kg CAE); p<0.01 significantly improved latency in the
vertical pole test compared to METH group. Meanwhile, Group III (300 mg/kg CAE);
p<0.001 and Group IV (500 mg/kg CAE); p<0.001 significantly decreased latency in the narrow
beam test compared to METH. Post-treatment of CAE on METH-treated rats, Group V (METH+300 mg/kg CAE) and
Group VI (METH+500 mg/kg CAE) non-significantly upregulated the SOD2 expression by 3.78±1.03 and 4.05±0.19
folds compared to METH, respectively. Post-treatment of CAE on METH-treated
rats, Group V
(METH+300 mg/kg CAE) and Group VI (METH+500 mg/kg CAE) non-significantly upregulated the miR-34a
expression by (7.02±3.73) and (6.75±1.94) folds compared to METH, respectively. CAE could be suggested as a promising
natural-derived therapeutic for METH-induced neurotoxicity to ameliorating
motor performance and triggering SOD2 and miR-34a expression.
Keywords: Centella asiatica; methamphetamine;
microRNA-34a; superoxide dismutase II
Abstrak
Keneurotoksikan
yang disebabkan oleh dadah psikostimulan, metafetamin (METH) dikaitkan dengan
kesan keneurotoksikan yang teruk dan berterusan pada sistem saraf pusat. Centella
asiatiaca (CA) terkenal sebagai agen antioksidan dan neurolindung. Walau
bagaimanapun, terdapat kajian yang terhad mengenai bahan teraputik semula jadi
untuk melemahkan keneurotoksikan yang disebabkan oleh METH. Kami berhasrat
mengkaji kesan METH dan ekstrak etanol CA (CAE) pada prestasi motor model
haiwan dan ekspresi manganese superoksida dismutase II (SOD2) dan mikroRNA-34a
(miR-34a) pada tisu otak. Tikus Sprague-Dawley jantan diberikan METH (50
mg/kg setiap berat badan) dua kali sehari selama 4 hari, CAE (300 mg/kg dan 500
mg/kg setiap berat badan) selama 21 hari dan gabungan METH dan CAE selama 21
hari. Berat tikus diukur dan prestasi motor dinilai menggunakan ujian kutub
menegak dan rasuk sempit. Ekspresi SOD2 dan miR-34a diukur menggunakan Real-time
Polymerase Chain Reaction (RT-qPCR). Kumpulan III (300 mg/kg CAE);
p<0.001, kumpulan V (METH+300 mg/kg CAE); p<0.01 dan kumpulan VI
(METH+500 mg/kg CAE); p<0.01, meningkatkan latensi secara signifikan dalam
ujian kutub menegak berbanding kumpulan METH. Manakala, kumpulan III (300 mg/kg
CAE); p<0.001 menurunkan latensi secara signifikan dalam ujian rasuk sempit
berbanding METH. Pasca rawatan CAE pada tikus yang dirawat dengan METH,
kumpulan V (METH+300 mg/kg CAE) dan kumpulan IV (METH+500 mg/kg CAE) secara
tidak signifikan meningkatkan ekspresi SOD2 berbanding METH iaitu masing-masing
pada 3.78±1.03 dan 4.05±0.19 ganda. Pasca rawatan CAE pada tikus yang dirawat
METH, kumpulan V (METH+300 mg/kg CAE) dan kumpulan VI (METH+500 mg/kg CAE)
secara tidak signifikan masing-masing meningkatkan ekspresi miR-34a (7.02±3.73
dan 6.75±1.94 ganda) berbanding METH. CAE boleh dicadangkan sebagai terapeutik
semula jadi yang menjanjikan untuk keneurotoksikan yang
disebabkan oleh METH untuk memperbaiki prestasi motor dan mencetuskan ekspresi
SOD2 dan miR-34a.
Kata kunci: Centella asiatica; metamfetamin;
mikroRNA-34a; superoksida dismutase II
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*Corresponding
author; email: shiha@uitm.edu.my
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