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

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...

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Main Author:	Shamsuddin, Nursyamila
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Pharmaceutical chemistry
Online Access:	https://ir.uitm.edu.my/id/eprint/57228/1/57228.pdf
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spelling	my-uitm-ir.572282022-05-19T14:08:13Z Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin 2020-05 Shamsuddin, Nursyamila Pharmaceutical chemistry 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 neurotoxicity. 2020-05 Thesis https://ir.uitm.edu.my/id/eprint/57228/ https://ir.uitm.edu.my/id/eprint/57228/1/57228.pdf text en public masters Universiti Teknologi MARA Faculty of Pharmacy Ahmad Noorden, Mohd Shihabuddin (Dr.)
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Ahmad Noorden, Mohd Shihabuddin (Dr.)
topic	Pharmaceutical chemistry
spellingShingle	Pharmaceutical chemistry Shamsuddin, Nursyamila Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
description	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 neurotoxicity.
format	Thesis
qualification_level	Master's degree
author	Shamsuddin, Nursyamila
author_facet	Shamsuddin, Nursyamila
author_sort	Shamsuddin, Nursyamila
title	Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
title_short	Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
title_full	Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
title_fullStr	Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
title_full_unstemmed	Neuroprotective effects of ethanolic extract of centella asiatica (CAE) on methamphetamine-induced neurotoxicity / Nursyamila Shamsuddin
title_sort	neuroprotective effects of ethanolic extract of centella asiatica (cae) on methamphetamine-induced neurotoxicity / nursyamila shamsuddin
granting_institution	Universiti Teknologi MARA
granting_department	Faculty of Pharmacy
publishDate	2020
url	https://ir.uitm.edu.my/id/eprint/57228/1/57228.pdf
_version_	1783734969049284608

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

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