Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase

Agriana Rosmalina Hidayati, Melinda, Hilkatul Ilmi, Takaya Sakura, Miako Sakaguchi, Junko Ohmori, Endah Dwi Hartuti, Lidya Tumewu, Daniel Ken Inaoka, Mulyadi Tanjung, Eri Yoshida, Fuyuki Tokumasu, Kiyoshi Kita, Mihoko Mori, Kazuyuki Dobashi, Tomoyoshi Nozaki, Din Syafruddin, Achmad Fuad Hafid, Danang Waluyo, Aty Widyawaruyanti

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2′, 4′, 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria.

Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalInternational Journal for Parasitology: Drugs and Drug Resistance
Volume21
DOIs
Publication statusPublished - Apr 2023

Keywords

  • Artocarpus altilis
  • Geranylated dihydrochalcone
  • PfMQO
  • Plasmodium falciparum
  • Ultrastructural changes

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