Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin

Shamsuddin, Nursyamila (2020) Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin. Masters thesis, Universiti Teknologi MARA.


Plant-derived antioxidants are known as promising therapeutic agent due to its
effectiveness and minimal side effects. Till today limited natural-derived antioxidant is
available to attenuate neurotoxicity induced by psychostimulant drug,
methamphetamine (METH). Persistence and long term abuse of METH promotes loss
of dopaminergic neurons which eventually results in neurodegenerative disorders
including Parkinson’s disease (PD). A traditional medicinal herb, Centella asiatica or
pegaga has been well studied to exert neuroprotective and antioxidant properties.
Herein, we examined potential neuroprotective effects of ethanolic extract of Centella
asiatica (CAE) on METH-induced neurotoxicity, in vitro all-trans retinoic acid (RA)
differentiated human neuroblastoma, SH-SY5Y cells and in vivo Sprague-Dawley rat
model. The RA-differentiated SH-SY5Y cells was used to resemble dopaminergic
neuronal-like cells. Cytotoxicity, neurotoxicity as well as neuroprotective effects of
CAE were measured via 3-(4,5- dimethylthiazol-2-yl)-5-(3-carboxymethoxypheyl)-2-
(4-sulfophenyl)-2H-tetrazolium, MTS assay against METH-treated SH-SY5Y cells.
Results showed that CAE significantly decreased the viability of the undifferentiated
SH-SY5Ycells in concentration-dependent manner. In addition, CAE (1mg/mL)
significantly increased the viability of neuron cells and did not caused toxic effects on
cells. CAE at concentrations of 100pg/mL and 1mg/mL conferred significant
neuroprotective effects against METH- induced neuronal-cell death. Meanwhile,
through in vivo Sprague-Dawley rat model, neuroprotective effects of CAE on PD-like
symptom was evaluated through behavioural test. Further, involvement of manganese
superoxide dismutase (SOD2) and microRNA, miR-34a in brain as antioxidant and
neuroprotection biomarker was measured by Quantitative Real-time Polymerase Chain
Reaction (qPCR). CAE treatment significantly improved the motor performance of
METH-treated rats as evaluated on vertical pole test and narrow beam test. Gene
expression showed that upregulation of SOD2 and miR-34a, suggest mechanism by
which CAE exerts its neuroprotective mechanisms against METH-induced
neurotoxicity. In conclusion, therefore we postulate that CAE could be promising
neuroprotective effects in in vitro and in vivo rat model of METH-induced


Item Type: Thesis (Masters)
Email / ID Num.
Shamsuddin, Nursyamila
Email / ID Num.
Thesis advisor
Ahmad Noorden, Mohd Shihabuddin (Dr.)
Subjects: R Medicine > RS Pharmacy and materia medica > Materia medica > Pharmaceutical chemistry
Divisions: Universiti Teknologi MARA, Shah Alam > Faculty of Pharmacy
Programme: Master of Science (Pharmacogenomics)
Keywords: Drug abuse; METH; clinical pharmacokinetics; molecular pharmacology; centella asiatica
Date: May 2020
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