{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:27:50Z","timestamp":1786343270616,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Parasitol."],"abstract":"\n Introduction<\/jats:title>\n \n Angiotensin II (Ang II) has been proposed to protect from severe malaria by killing the parasite and maintaining the blood-brain barrier integrity by acting through type 1 (AT\n 1<\/jats:sub>\n R) and type 2 (AT\n 2<\/jats:sub>\n R) receptors. However, this protection from severe malaria is counterproductive in adulthood as the elevated plasma Ang II puts the individual at risk for developing hypertension. Various natural and synthetic peptides of Ang II have been explored to check its antiplasmodial actions despite Ang II being a significant vasopressor via its actions through AT\n 1<\/jats:sub>\n R. Therefore, to be able to explore Ang II as a potential antiplasmodial agent, it is important to demonstrate its IC\n 50<\/jats:sub>\n against\n P. falciparum in vitro<\/jats:italic>\n and its minimum effective concentration required for activation of AT\n 1<\/jats:sub>\n R. It is desirable that IC\n 50<\/jats:sub>\n of Ang II against\n P. falciparum<\/jats:italic>\n remains below the threshold for AT\n 1<\/jats:sub>\n R activation and hence to verify this, the current study was planned as there are no previously published reports for determining the threshold Ang II concentration for AT\n 1<\/jats:sub>\n R activation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n For invasion inhibition assay, Pf-infected RBCs (schizonts) were incubated with four different concentrations of Ang II for 16 hours. The activation of AT\n 1<\/jats:sub>\n R and AT\n 2<\/jats:sub>\n R in the presence of Ang II (from 10\n \u20139<\/jats:sup>\n M to 10\n \u20137<\/jats:sup>\n M) was tested by calcium and cGMP signaling assays, respectively using the human brain microvascular endothelial cell line as an\n in vitro<\/jats:italic>\n model.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Effective Ang II concentration among all tested concentrations was found to be 10\n \u20136<\/jats:sup>\n M against\n Plasmodium falciparum<\/jats:italic>\n invasion. Statistically non-significant and negligible responses in AT\n 1<\/jats:sub>\n R and AT\n 2<\/jats:sub>\n R activation were observed below the desired Ang II concentration of 10\n \u20136<\/jats:sup>\n M.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n The results indicate that the IC\n 50<\/jats:sub>\n of Ang II against\n P. falciparum<\/jats:italic>\n is below the threshold for AT\n 1<\/jats:sub>\n R activation. However, the minimum effective Ang II concentration required for AT\n 1<\/jats:sub>\n R activation remains unanswered which demands further improvement in experimental designs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fpara.2026.1852476","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:30:16Z","timestamp":1786339816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating angiotensin II concentration in modulating Plasmodium falciparum infection and angiotensin receptor activation"],"prefix":"10.3389","volume":"5","author":[{"given":"Auley","family":"De","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Indian Council of Medical Research (ICMR)-National Institute of Malaria Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Indian Council of Medical Research (ICMR)-National Institute of Malaria Research","place":["New Delhi, India"]},{"name":"Department of Biotechnology, Bhimtal, Kumaun University","place":["Uttarakhand, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medha","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Indian Council of Medical Research (ICMR)-National Institute of Malaria Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Pande","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bhimtal, Kumaun University","place":["Uttarakhand, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Indian Council of Medical Research (ICMR)-National Institute of Malaria Research","place":["New Delhi, India"]},{"name":"Department of Epidemiology, Academy of Scientific and Innovative Research","place":["Ghaziabad, UP, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12070900","article-title":"Cultivation of asexual intraerythrocytic stages of Plasmodium falciparum","volume":"12","author":"Basco","year":"2023","journal-title":"Pathogens"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1161\/01.atv.15.10.1646","article-title":"Angiotensin II increases cGMP content via endothelial angiotensin II AT1 subtype receptors in the rat carotid artery","volume":"15","author":"Caputo","year":"1995","journal-title":"Arterioscler. 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