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.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ANOVA:
-
One-way analysis of variance
- BBB:
-
Blood brain barrier
- CM:
-
Cerebral malaria
- CMC:
-
Carboxymethyl cellulose
- COX-2:
-
Cyclooxygenase-2
- CPCSEA:
-
Committee for the Purpose of Control and Supervision of Experiments on Animals
- DPX:
-
Dibutylphthalate polystyrene xylene
- ECM:
-
Experimental cerebral malaria
- EPM:
-
Elevated plus maze
- ICAM-1:
-
Intercellular adhesion molecule 1
- IFN ‐γ:
-
Interferon-gamma
- IL-1β:
-
Interleukin-1 beta
- iNOS:
-
Inducible nitric oxide synthase
- LPS:
-
Lipopolysaccharide
- NF-kB:
-
Nuclear factor kappa B
- NLRP3:
-
NOD-, LRR- and pyrin domain-containing protein 3)
- NO:
-
Nitric Oxide
- OsO4 :
-
Osmium tetroxide
- pRBCs:
-
Parasitized red blood cells
- QNN-T:
-
Quinine treated
- RBCs:
-
Red blood cells
- SPSS:
-
Statistical package for the social sciences
- TLR 4:
-
Toll-like receptor 4
- TNF-α:
-
Tumour necrosis factor alpha
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Acknowledgements
We are thankful to ICMR, New Delhi for providing financial support in form of junior research fellowship and senior research fellowship to Shweta Sinha. Special thanks are given to Upma Bagai, Professor, Punjab University, Chandigarh for providing the P. berghei ANKA strain and technical staff of CSIC, Post Graduate Institute of Medical Education & Research, Chandigarh, India, for allowing the use of sophisticated instruments.
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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RS, BM, BDR and SS designed the study. SS carried out the experiment and wrote the initial draft of the manuscript. BDR examined the Histopathological and IHC Data. All authors SS, RS, BDR, BM, DIB and NM did the final editing of manuscript and agreed to the publication of this study.
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The ethical approval was taken from the Institutional Animal Ethics Committee, Postgraduate Institute of Medical Education and Research, Chandigarh, Reference No. 69/IAEC/418 as per the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines.
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13205_2023_3676_MOESM1_ESM.jpg
Supplementary File 1. Induced CM in C57BL/6 mice. Step 1: Inoculation of 0.2 mL containing 106 of P. berghei ANKA infected erythrocytes. Step 2: A) Thin smear of P. berghei ANKA infected erythrocytes stained with Giemsa and observed under 1000 X oil immersion on 10th post-infection. B) Graph to show linear progression of infection in terms of percentage parasitemia from day 3rd till 10th post-infection. ***p<0.001 vs day 3rd post-infection (n=3). Step 3: Histopathological features of tissues stained with hematoxylin and eosin : A) Brain at 400 X magnification B) Brain at 1000X magnification and C) Liver D) Spleen E)Lung F)Kidney sections of P. berghei ANKA infected mice model at 400 X magnifications. The black arrow indicates deposition of malaria pigment (hemozoin) (JPG 149 KB)
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Sinha, S., Medhi, B., Radotra, B.D. et al. Evaluation of chalcone derivatives for their role as antiparasitic and neuroprotectant in experimentally induced cerebral malaria mouse model. 3 Biotech 13, 260 (2023). https://doi.org/10.1007/s13205-023-03676-y
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DOI: https://doi.org/10.1007/s13205-023-03676-y