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Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells

Mesenchymal stem cells (MSCs) have seen an elevated use in clinical works like regenerative medicine. Its potential therapeutic properties increases when used in tandem with complementary agents like bio-based materials. Therefore, the present study is the first to investigate the cytotoxicity of a...

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Main Authors: Ramarao, Kivaandra Dayaa Rao, Somasundram, Chandran, Razali, Zuliana, Kunasekaran, Wijenthiran, Jin, Tan Li, Musa, Sabri, Achari, Vijayan Manickam
Format: Article
Published: Public Library of Science 2022
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RS Pharmacy and materia medica
Online Access:http://eprints.um.edu.my/40642/
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spelling my.um.eprints.406422023-10-20T01:32:17Z http://eprints.um.edu.my/40642/ Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells Ramarao, Kivaandra Dayaa Rao Somasundram, Chandran Razali, Zuliana Kunasekaran, Wijenthiran Jin, Tan Li Musa, Sabri Achari, Vijayan Manickam RS Pharmacy and materia medica Mesenchymal stem cells (MSCs) have seen an elevated use in clinical works like regenerative medicine. Its potential therapeutic properties increases when used in tandem with complementary agents like bio-based materials. Therefore, the present study is the first to investigate the cytotoxicity of a highly valued medicinal plant, Moringa oleifera, on human Wharton's Jelly mesenchymal stem cells (hWJMSCs) and its effects on the cells' gene expression when used as a pre-treatment agent in vitro. M. oleifera leaves (MOL) were dried and subjected to UHPLC-QTOF/MS analysis, revealing several major compounds like apigenin, kaempferol, and quercetin in the MOL, with various biological activities like antioxidant and anti-cancer properties. We then treated the hWJMSCs with MOL and noticed a dose-dependant inhibition on the cells' proliferation. RNA-sequencing was performed to explain the possible mechanism of action and revealed genes like PPP1R1C, SULT2B1, CDKN1A, mir-154 and CCNB1, whose expression patterns were closely associated with the negative cell cycle regulation and cell cycle arrest process. This is also evident from gene set enrichment analysis where the GO and KEGG terms for down-regulated pathways were closely related to the cell cycle regulation. The Ingenuity pathway analysis (IPA) software further predicted the significant activation of (p < 0.05, z-score > 2) of the G2/M DNA damage checkpoint regulation pathway. The present study suggests that MOL exhibits an antiproliferative effect on hWJMSCs via cell cycle arrest and apoptotic pathways. We believe that this study provides an important baseline reference for future works involving MOL's potential to accompany MSCs for clinical works. Future works can take advantage of the cell's strong anti-cancer gene expression found in this study, and evaluate our MOL treatment on various cancer cell lines. Public Library of Science 2022-10 Article PeerReviewed Ramarao, Kivaandra Dayaa Rao and Somasundram, Chandran and Razali, Zuliana and Kunasekaran, Wijenthiran and Jin, Tan Li and Musa, Sabri and Achari, Vijayan Manickam (2022) Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells. PLoS ONE, 17 (10). ISSN 1932-6203, DOI https://doi.org/10.1371/journal.pone.0274814 <https://doi.org/10.1371/journal.pone.0274814>. 10.1371/journal.pone.0274814
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic RS Pharmacy and materia medica
spellingShingle RS Pharmacy and materia medica
Ramarao, Kivaandra Dayaa Rao
Somasundram, Chandran
Razali, Zuliana
Kunasekaran, Wijenthiran
Jin, Tan Li
Musa, Sabri
Achari, Vijayan Manickam
Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
description Mesenchymal stem cells (MSCs) have seen an elevated use in clinical works like regenerative medicine. Its potential therapeutic properties increases when used in tandem with complementary agents like bio-based materials. Therefore, the present study is the first to investigate the cytotoxicity of a highly valued medicinal plant, Moringa oleifera, on human Wharton's Jelly mesenchymal stem cells (hWJMSCs) and its effects on the cells' gene expression when used as a pre-treatment agent in vitro. M. oleifera leaves (MOL) were dried and subjected to UHPLC-QTOF/MS analysis, revealing several major compounds like apigenin, kaempferol, and quercetin in the MOL, with various biological activities like antioxidant and anti-cancer properties. We then treated the hWJMSCs with MOL and noticed a dose-dependant inhibition on the cells' proliferation. RNA-sequencing was performed to explain the possible mechanism of action and revealed genes like PPP1R1C, SULT2B1, CDKN1A, mir-154 and CCNB1, whose expression patterns were closely associated with the negative cell cycle regulation and cell cycle arrest process. This is also evident from gene set enrichment analysis where the GO and KEGG terms for down-regulated pathways were closely related to the cell cycle regulation. The Ingenuity pathway analysis (IPA) software further predicted the significant activation of (p < 0.05, z-score > 2) of the G2/M DNA damage checkpoint regulation pathway. The present study suggests that MOL exhibits an antiproliferative effect on hWJMSCs via cell cycle arrest and apoptotic pathways. We believe that this study provides an important baseline reference for future works involving MOL's potential to accompany MSCs for clinical works. Future works can take advantage of the cell's strong anti-cancer gene expression found in this study, and evaluate our MOL treatment on various cancer cell lines.
format Article
author Ramarao, Kivaandra Dayaa Rao
Somasundram, Chandran
Razali, Zuliana
Kunasekaran, Wijenthiran
Jin, Tan Li
Musa, Sabri
Achari, Vijayan Manickam
author_facet Ramarao, Kivaandra Dayaa Rao
Somasundram, Chandran
Razali, Zuliana
Kunasekaran, Wijenthiran
Jin, Tan Li
Musa, Sabri
Achari, Vijayan Manickam
author_sort Ramarao, Kivaandra Dayaa Rao
title Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
title_short Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
title_full Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
title_fullStr Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
title_full_unstemmed Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton's Jelly mesenchymal stem cells
title_sort antiproliferative effects of dried moringa oleifera leaf extract on human wharton's jelly mesenchymal stem cells
publisher Public Library of Science
publishDate 2022
url http://eprints.um.edu.my/40642/
_version_ 1781704522214670336
score 13.211869

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