Evaluation of chalcone derivatives for their role as antiparasitic and neuroprotectant in experimentally induced cerebral malaria mouse model

Shweta Sinha; Bikash Medhi; B D Radotra; Daniela Batovska; Nadezhda Markova; Rakesh Sehgal

doi:10.1007/s13205-023-03676-y

Evaluation of chalcone derivatives for their role as antiparasitic and neuroprotectant in experimentally induced cerebral malaria mouse model

3 Biotech. 2023 Jul;13(7):260. doi: 10.1007/s13205-023-03676-y. Epub 2023 Jul 1.

Authors

Shweta Sinha¹, Bikash Medhi², B D Radotra³, Daniela Batovska⁴, Nadezhda Markova⁴, Rakesh Sehgal¹

Affiliations

¹ Department of Medical Parasitology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012 India.
² Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
³ Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
⁴ Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.

PMID: 37405268
PMCID: PMC10314887 (available on 2024-07-01)
DOI: 10.1007/s13205-023-03676-y

Abstract

Cerebral malaria is a severe complication of Plasmodium falciparum infection with a complex pathophysiology. The current course of treatment is ineffective in lowering mortality or post-treatment side effects such as neurological and cognitive abnormalities. Chalcones are enormously distributed in spices, fruits, vegetables, tea, and soy-based foodstuffs that are well known for their antimalarial activity, and in recent years they have been widely explored for brain diseases like Alzheimer's disease. Therefore, considering the previous background of chalcones serving as both antimalarial and neuroprotective, the present study aimed to study the effect of these chalcone derivatives on an experimental model of cerebral malaria (CM). CM-induced mice were tested behaviorally (elevated plus maze, rota rod test, and hanging wire test), biochemically (nitric oxide estimation, cytokines (IL-1, IL-6, IL-10, IL-12p70, TNF, IFN-y), histopathologically and immunohistochemically, and finally ultrastructural changes were examined using a transmission electron microscope. All three chalcones treated groups showed a significant (p < 0.001) decrease in percentage parasitemia at the 10th day post-infection. Mild anxiolytic activity of chalcones as compared to standard treatment with quinine has been observed during behavior tests. No pigment deposition was observed in the QNN-T group and other chalcone derivative treated groups. Rosette formation was seen in the derivative 1 treated group. The present derivatives may be pioneered by various research and science groups to design such a scaffold that will be a future antimalarial with therapeutic potential or, because of its immunomodulatory properties, it could be used as an adjunct therapy.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-023-03676-y.

Keywords: Cerebral malaria; Chalcones; In vivo; P. falciparum; Treatment.

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