2. Academic Validation
  3. Brazilin and its oxidized form "brazilein", the natural fluorescently traceable agents, toxify Plasmodium falciparum to pyknotic death via disrupting its iron homeostasis

Brazilin and its oxidized form "brazilein", the natural fluorescently traceable agents, toxify Plasmodium falciparum to pyknotic death via disrupting its iron homeostasis

  • Free Radic Biol Med. 2026 May:248:367-385. doi: 10.1016/j.freeradbiomed.2026.02.073.
Mattapong Kulaphisit 1,  Wannakan Jaikamlue 2,  Natnapa Jaitan 3,  Jitnapa Sirirak 4,  Poomipat Tamdee 4,  Kumpanat Pomlok 2,  Chanida Chumchanchira 2,  Sakunthip Changkhong 2,  Jiraprapa Wipasa 5,  Chalermpong Saenjum 6,  Pathrapol Lithanatudom 7
Affiliations

Affiliations

  • 1 Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand; Research Center for Innovation in Analytical Science and Technology for Biodiversity-based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 2 Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 3 Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; PhD Degree Program in Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 4 Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom, 73000, Thailand.
  • 5 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 6 Research Center for Innovation in Analytical Science and Technology for Biodiversity-based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: [email protected].
  • 7 Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; Research Center for Innovation in Analytical Science and Technology for Biodiversity-based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: [email protected].
PMID: 41771360 DOI: 10.1016/j.freeradbiomed.2026.02.073
Abstract

A paradigm shift from malaria prevention to eradication requires more effective drug discovery. To cope with the emergence of anti-malarial drug resistance, screening for novel mode (s) of mechanism against Plasmodium falciparum (Pf) is indispensable. Here, we develop the algorithm of Multispectral Imaging Flow Cytometry (MIFC) for precisely detecting parasitemia, stage differentiation and survivability in Pf. Using this approach, we discovered a decoction made from Caesalpinia sappan L. (CS) heartwood, serves as a promising novel anti-plasmodial activity. While brazilin was characterized as the major active compound, its more stably oxidized form in the water-soluble environment "brazilein" is capable of binding Fe2+. High-resolution confocal imaging analyses revealed reversible fluorescence traceability of both brazilin and brazilein, led to real-time monitoring of their transformation (brazilin-brazilein) and anti-plasmodial property. Mechanistically, brazilein coordinately binds to labile Fe2+ pools within Pf and red blood cells. Subsequently, brazilein further infiltrates into Hemoglobin and this complex also binds to the active site of apical membrane antigen 1 (AMA1), resulting in inhibitions of Hemoglobin digestion and erythrocyte invasion, respectively. These disruption of iron homeostasis eventually induces pyknotic death as evidenced by holotomography and MIFC. Taken together, brazilein is a remarkable natural active pharmaceutical ingredient which possesses a real-time tracking capability allowing for elucidating its novel anti-plasmodial activity.

Keywords

Anti-plasmodial activity; Brazilein; Brazilin; Caesalpinia sappan; Ethnomedicine; Iron chelation; Plasmodium falciparum.

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