The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum

Malaria caused by Plasmodium parasites has afflicted humans since ancient times. Due to the prevalence of drug-resistant P. falciparum, the effectiveness of the standard antimalarial drugs has decreased, requiring research into the development of new antimalarial drugs with novel targets. Ellagic ac...

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Main Author:	Thuduhena, Thuduhenage Dona Anjana Chamilka
Format:	Thesis
Language:	English
Published:	2024
Subjects:	G Geography Anthropology Recreation R Medicine RC109-216 Infectious and parasitic diseases
Online Access:	http://eprints.usm.my/61034/1/THUDUHENAGE%20DONA%20ANJANA%20CHAMILKA%20THUDUHENA-FT%20P-SKM000121%28R%29-E.pdf
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spelling	my-usm-ep.610342024-10-13T02:51:53Z The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum 2024-04 Thuduhena, Thuduhenage Dona Anjana Chamilka G Geography. Anthropology. Recreation R Medicine RC109-216 Infectious and parasitic diseases Malaria caused by Plasmodium parasites has afflicted humans since ancient times. Due to the prevalence of drug-resistant P. falciparum, the effectiveness of the standard antimalarial drugs has decreased, requiring research into the development of new antimalarial drugs with novel targets. Ellagic acid has been shown to have antimalarial activity against P. falciparum in vitro by inhibiting the formation of beta-haematin (haemozoin) in the mature stage parasite. The present study aimed to elucidate the mechanism of antimalarial action of ellagic acid on haemoglobin ingestion, transport and digestion in chloroquine-sensitive (3D7) and chloroquine-resistant (W2) strains of P. falciparum in vitro. The antimalarial activity of ellagic acid that inhibits 50% of the parasite population (IC50) was determined using a malarial SYBR Green I fluorescence-based (MSF) assay with artemisinin was used as a standard drug. Based on the IC50 value of ellagic acid, early trophozoite stage parasites were incubated with the compound at different concentrations for 8 hours before Giemsa-stained thin blood smears were prepared and viewed by light microscopy. The concentrations of 3.0 and 3.9 nM were selected to observe the maximum effect of ellagic acid on early trophozoite stage of 3D7 and W2 parasites, respectively by transmission electron microscopy. Jasplakinolide (7 μM) and E-64 (10μM) were used as control drugs. The results show that ellagic acid significantly inhibited (p < 0.001) 3D7 and W2 parasites with IC50 values of 1.0 ± 0.7 and 1.3 ± 0.1 nM, respectively as compared with artemisinin (IC50-3D7 parasite = 2.2 ± 0.2 nM; IC50-W2 parasite = 4.3 ± 0.3 nM). The results show that shrunken parasites were observed in all ellagic acid-treated groups of 3D7 and W2 parasites. The results show the formation of 3D7: 3 ± 2 and W2: 4 ± 2 haemoglobin-containing cytostomal sections, indicating the inhibition of haemoglobin uptake in the ellagic acid-treated 3D7 and W2 parasites. Only 3 ± 1 cytostomal sections were observed in the jasplakinolide-treated 3D7 parasite, 2 ± 1 cytostomal section was observed in the jasplakinolide-treated W2 parasite. The haemoglobin-containing transport vesicle was not observed in the ellagic acid and jasplakinolide-treated 3D7 and W2 parasites. As compared with the control of non-treated parasites, the high contrast and enlarged digestive vacuole was observed in the ellagic acid and E-64-treated 3D7 and W2 parasites. In conclusion, ellagic acid has the potential to be a new antimalarial drug targeting haemoglobin ingestion, transport and digestion of chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. 2024-04 Thesis http://eprints.usm.my/61034/ http://eprints.usm.my/61034/1/THUDUHENAGE%20DONA%20ANJANA%20CHAMILKA%20THUDUHENA-FT%20P-SKM000121%28R%29-E.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	G Geography Anthropology Recreation R Medicine RC109-216 Infectious and parasitic diseases
spellingShingle	G Geography Anthropology Recreation R Medicine RC109-216 Infectious and parasitic diseases Thuduhena, Thuduhenage Dona Anjana Chamilka The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
description	Malaria caused by Plasmodium parasites has afflicted humans since ancient times. Due to the prevalence of drug-resistant P. falciparum, the effectiveness of the standard antimalarial drugs has decreased, requiring research into the development of new antimalarial drugs with novel targets. Ellagic acid has been shown to have antimalarial activity against P. falciparum in vitro by inhibiting the formation of beta-haematin (haemozoin) in the mature stage parasite. The present study aimed to elucidate the mechanism of antimalarial action of ellagic acid on haemoglobin ingestion, transport and digestion in chloroquine-sensitive (3D7) and chloroquine-resistant (W2) strains of P. falciparum in vitro. The antimalarial activity of ellagic acid that inhibits 50% of the parasite population (IC50) was determined using a malarial SYBR Green I fluorescence-based (MSF) assay with artemisinin was used as a standard drug. Based on the IC50 value of ellagic acid, early trophozoite stage parasites were incubated with the compound at different concentrations for 8 hours before Giemsa-stained thin blood smears were prepared and viewed by light microscopy. The concentrations of 3.0 and 3.9 nM were selected to observe the maximum effect of ellagic acid on early trophozoite stage of 3D7 and W2 parasites, respectively by transmission electron microscopy. Jasplakinolide (7 μM) and E-64 (10μM) were used as control drugs. The results show that ellagic acid significantly inhibited (p < 0.001) 3D7 and W2 parasites with IC50 values of 1.0 ± 0.7 and 1.3 ± 0.1 nM, respectively as compared with artemisinin (IC50-3D7 parasite = 2.2 ± 0.2 nM; IC50-W2 parasite = 4.3 ± 0.3 nM). The results show that shrunken parasites were observed in all ellagic acid-treated groups of 3D7 and W2 parasites. The results show the formation of 3D7: 3 ± 2 and W2: 4 ± 2 haemoglobin-containing cytostomal sections, indicating the inhibition of haemoglobin uptake in the ellagic acid-treated 3D7 and W2 parasites. Only 3 ± 1 cytostomal sections were observed in the jasplakinolide-treated 3D7 parasite, 2 ± 1 cytostomal section was observed in the jasplakinolide-treated W2 parasite. The haemoglobin-containing transport vesicle was not observed in the ellagic acid and jasplakinolide-treated 3D7 and W2 parasites. As compared with the control of non-treated parasites, the high contrast and enlarged digestive vacuole was observed in the ellagic acid and E-64-treated 3D7 and W2 parasites. In conclusion, ellagic acid has the potential to be a new antimalarial drug targeting haemoglobin ingestion, transport and digestion of chloroquine-sensitive and chloroquine-resistant strains of P. falciparum.
format	Thesis
qualification_level	Master's degree
author	Thuduhena, Thuduhenage Dona Anjana Chamilka
author_facet	Thuduhena, Thuduhenage Dona Anjana Chamilka
author_sort	Thuduhena, Thuduhenage Dona Anjana Chamilka
title	The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
title_short	The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
title_full	The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
title_fullStr	The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
title_full_unstemmed	The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
title_sort	mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2024
url	http://eprints.usm.my/61034/1/THUDUHENAGE%20DONA%20ANJANA%20CHAMILKA%20THUDUHENA-FT%20P-SKM000121%28R%29-E.pdf
_version_	1818647369115238400

The mechanism of antimalarial action of ellagic acid on haemoglobin metabolism in plasmodium falciparum

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