Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman

Centella asiatica (C. asiatica), locally known as 'pegaga', is a herb used in traditional Chinese medicine to treat various diseases, including cancer. There is, however, no information on its potential anti-leukaemic activity. Thus, this study investigated the underlying mechanism of anti...

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Main Author:	Othman, Norodiyah
Format:	Thesis
Language:	English
Published:	2022
Subjects:	Diseases of the blood and blood-forming organs Medicinal plants (Culture only)
Online Access:	https://ir.uitm.edu.my/id/eprint/75494/1/75494.pdf
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id	my-uitm-ir.75494
record_format	uketd_dc
spelling	my-uitm-ir.754942024-06-24T04:30:45Z Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman 2022 Othman, Norodiyah Diseases of the blood and blood-forming organs Medicinal plants (Culture only) Centella asiatica (C. asiatica), locally known as 'pegaga', is a herb used in traditional Chinese medicine to treat various diseases, including cancer. There is, however, no information on its potential anti-leukaemic activity. Thus, this study investigated the underlying mechanism of anti-leukaemic activity of C. asiatica ethanolic extract and triterpenoids (madecassoside; ME, asiaticoside; AE, madecassic acid; MA, asiatic acid; AA) on human CCRF-CEM T-acute lymphoblastic leukaemia (T-ALL) cells through in silico and in vitro methods. A ligand-based target prediction model comprising 26 leukaemia-related targets and 26,540 compounds was first built using a random forest algorithm. The model was validated through internal and external validation. Molecular docking was then performed on the targets predicted for the triterpenoids. The in vitro anti-proliferative activity was evaluated by assessing the cell apoptosis rate using annexin-V flowcytometry. The intracellular reactive oxygen species (ROS) level and mitochondrial membrane change (MMP) were measured using fluorescence analysis. At the molecular level, the gene expression profile was assessed by microarray, followed by an analysis of protein-protein interaction and gene enrichment functional analysis. In addition, the protein expression level of the apoptosis-related gene was determined using western blot analysis. The built prediction model, named the Leuk- RP model, showed an average sensitivity, specificity and accuracy of 87.4%, 95.0% and 91.8%), respectively. In the external validation, the model showed an average sensitivity, specificity and accuracy of 89.8%>, 87.5% and 81.9%, respectively. The triterpenoids were predicted to bind to SLC29A1, TNFa, and NR3C1 with different scores. Docking results demonstrated that the triterpenoids could bind to TNFa active site, with binding energies ranging from -9.0 to -9.5 kcal/mol. 2022 Thesis https://ir.uitm.edu.my/id/eprint/75494/ https://ir.uitm.edu.my/id/eprint/75494/1/75494.pdf text en public phd doctoral Universiti Teknologi MARA (UiTM) Faculty of Pharmacy Mohd Fauzi, Fazlin
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Mohd Fauzi, Fazlin
topic	Diseases of the blood and blood-forming organs Medicinal plants (Culture only)
spellingShingle	Diseases of the blood and blood-forming organs Medicinal plants (Culture only) Othman, Norodiyah Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
description	Centella asiatica (C. asiatica), locally known as 'pegaga', is a herb used in traditional Chinese medicine to treat various diseases, including cancer. There is, however, no information on its potential anti-leukaemic activity. Thus, this study investigated the underlying mechanism of anti-leukaemic activity of C. asiatica ethanolic extract and triterpenoids (madecassoside; ME, asiaticoside; AE, madecassic acid; MA, asiatic acid; AA) on human CCRF-CEM T-acute lymphoblastic leukaemia (T-ALL) cells through in silico and in vitro methods. A ligand-based target prediction model comprising 26 leukaemia-related targets and 26,540 compounds was first built using a random forest algorithm. The model was validated through internal and external validation. Molecular docking was then performed on the targets predicted for the triterpenoids. The in vitro anti-proliferative activity was evaluated by assessing the cell apoptosis rate using annexin-V flowcytometry. The intracellular reactive oxygen species (ROS) level and mitochondrial membrane change (MMP) were measured using fluorescence analysis. At the molecular level, the gene expression profile was assessed by microarray, followed by an analysis of protein-protein interaction and gene enrichment functional analysis. In addition, the protein expression level of the apoptosis-related gene was determined using western blot analysis. The built prediction model, named the Leuk- RP model, showed an average sensitivity, specificity and accuracy of 87.4%, 95.0% and 91.8%), respectively. In the external validation, the model showed an average sensitivity, specificity and accuracy of 89.8%>, 87.5% and 81.9%, respectively. The triterpenoids were predicted to bind to SLC29A1, TNFa, and NR3C1 with different scores. Docking results demonstrated that the triterpenoids could bind to TNFa active site, with binding energies ranging from -9.0 to -9.5 kcal/mol.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Othman, Norodiyah
author_facet	Othman, Norodiyah
author_sort	Othman, Norodiyah
title	Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
title_short	Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
title_full	Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
title_fullStr	Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
title_full_unstemmed	Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman
title_sort	elucidating the mechanism of action of centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / norodiyah othman
granting_institution	Universiti Teknologi MARA (UiTM)
granting_department	Faculty of Pharmacy
publishDate	2022
url	https://ir.uitm.edu.my/id/eprint/75494/1/75494.pdf
_version_	1804889693993566208

Elucidating the mechanism of action of Centella asiatica ethanolic extract and triterpenoids as a potential anti-leukaemic agent through the integration of in silico and in vitro studies / Norodiyah Othman

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