{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:36:02Z","timestamp":1787070962532,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n Context:<\/jats:title>\n \n Malaria, caused by\n Plasmodium<\/jats:italic>\n parasites, has been a persistent threat to human health for centuries, causing significant illnesses and fatalities. The rise of drug-resistant strains has diminished the efficacy of conventional antimalarial medications, necessitating the exploration of alternative treatments. Ellagic acid has emerged as a promising candidate, demonstrating effectiveness in laboratory experiments by impeding beta-hematin (hemozoin) formation in mature\n Plasmodium falciparum<\/jats:italic>\n stages. This research endeavors to elucidate the ellagic acid\u2019s mechanism of action against malaria parasites by examining its impact on hemoglobin ingestion, transport, and digestion in both chloroquine-sensitive (3D7) and chloroquine-resistant (W2)\n P. falciparum<\/jats:italic>\n strains\n in vitro<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Aim:<\/jats:title>\n \n This study aimed to elucidate the mechanism of ellagic acid antimalarial action against 3D7 and W2 strains of\n P. falciparum in vitro<\/jats:italic>\n by using a transmission electron microscope.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n 3D7 and W2 strains of\n P. falciparum<\/jats:italic>\n were cultured in flasks with a complete culture medium and washed red blood cells (type O\n +<\/jats:sup>\n ) at a hematocrit of 2%. Synchronized ring-stage parasite-infected erythrocytes, approximately 2 h post-synchronization, were utilized for the antimalarial activity assay. Based on the half-maximal inhibitory concentration (IC\n 50<\/jats:sub>\n ) value of ellagic acid, three different sub-lethal concentrations of the compound against the 3D7 and W2 strains. Samples were prepared for real-time microscopic analysis. Samples were immediately fixed in 2.5% glutaraldehyde in 0.2 M phosphate buffer (pH 7.4) for 2 h. Then, the samples were washed, postfixed with 2% osmium tetroxide in 0.1 M phosphate buffer for 1 h, washed with distilled water, dehydrated, infiltrated, and embedded. The sample blocks were cut by using an ultramicrotome. These thin sections were stained with 1% lead citrate and 1% uranyl acetate.\n <\/jats:p>\n <\/jats:sec>\n \n Statistical Analysis Used:<\/jats:title>\n \n The IC\n 50<\/jats:sub>\n of ellagic acid against the 3D7 and W2 parasites was analyzed using computerized GraphPad Prism 8.0 software.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Findings show significant inhibition by ellagic acid (\n P<\/jats:italic>\n < 0.001) against 3D7 and W2 parasites. The IC\n 50<\/jats:sub>\n values were 1.0 \u00b1 0.7 and 1.3 \u00b1 0.1 nM, respectively, surpassing the artemisinin\u2019s effectiveness (IC\n 50-3D7 parasite<\/jats:sub>\n = 2.2 \u00b1 0.2 nM; IC\n 50-W2 parasite<\/jats:sub>\n = 4.3 \u00b1 0.3 nM). Transmission electron microscopy elucidated the ellagic acid\u2019s impact on the early trophozoite stage of 3D7 and W2 parasites, highlighting the disruption of hemoglobin metabolism within the parasites.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n These findings underscore the ellagic acid\u2019s potential as a promising antimalarial agent, targeting hemoglobin processes in both 3D7 and W2\n P. falciparum<\/jats:italic>\n strains.\n <\/jats:p>\n <\/jats:sec>\n \n Key Messages:<\/jats:title>\n Malaria is an important public health disease in the world. Ellagic acid is most active in the late stage of the malaria parasites during which the host cell hemoglobin is ingested and digested.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/jmau.jmau_96_24","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:57Z","timestamp":1732838457000},"page":"210-226","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Ellagic Acid on Hemoglobin Ingestion, Transport, and Digestion in the Digestive Vacuole of Plasmodium falciparum"],"prefix":"10.4103","volume":"13","author":[{"given":"Anjana Chamilka","family":"Thuduhena","sequence":"first","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurhidanatasha","family":"Abu-Bakar","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Nasuha","family":"Hamzah","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"R2-20251212","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD007483.pub2","article-title":"Artemisinin-based combination therapy for treating uncomplicated malaria","author":"Sinclair","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"R3-20251212","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1242\/jcs.023150","article-title":"A new model for hemoglobin ingestion and transport by the human malaria parasite Plasmodium falciparum","volume":"121","author":"Lazarus","year":"2008","journal-title":"J Cell 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