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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
Diserahkan: 20 Mei 2022/Diterima:
23 Ogos 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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*Pengarang untuk surat-menyurat; email: shiha@uitm.edu.my
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