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Background <p>Chemotherapy is a crucial part of cancer treatment, but it has been linked to a set of cognitive impairments. 5-Fluorouracil, a chemotherapeutic drug causing mitochondrial dysfunction and neurodegeneration. This study primarily aimed to evaluate the effect of Plumbagin on mitochondrial dynamics, neuroinflammation and oxidative stress in adult zebrafish subjected to 5-Fluorouracil-induced cognitive impairment.</p> Material and Methods <p>In this study, initially <i>in-silico</i> studies were conducted for lead compound identification. For the <i>in-vivo</i>&#xa0;studies, adult zebrafish (~ 6–8&#xa0;months old; 470–530&#xa0;mg; 126 animals are used) were randomly assigned to 7 groups and treated with 5-Fluorouracil (25&#xa0;mg/kg; <i>i.p.</i>) for 1&#xa0;day followed by post-treated with Plumbagin (10 and 20&#xa0;mg/kg; <i>i.p.</i>) and Donepezil (5&#xa0;mg/kg; <i>i.p.</i>) for 6&#xa0;days. Behavioral, biochemical, molecular, mitochondrial, and histopathological analyses were performed after completion of the study.</p> Result <p><i>In-silico</i> analyses revealed that Plumbagin exhibits stronger binding affinity as compared to 5-Fluorouracil. In vivo findings further demonstrated that post-treatment with Plumbagin significantly mitigates oxidative stress markers, reduces neuroinflammatory cytokines, and enhances mitochondrial functioning (mitochondrial enzyme complexes, caspases-3, and cellular viability) relative to zebrafish treated with 5-Flurouracil alone. Additionally, Plumbagin treatment led to marked reduction in GSK-3β expression, improvements in mitochondrial structure (as observed through Transmission electron microscopy analysis. Further, post-treatment with Plumbagin significantly improved mitochondrial morphology (as observed through TEM analysis) and neuronal morphology (assessed via Hematoxylin and Eosin staining and Nissl staining) as compared to 5-Fluorouracil -treated zebrafish.</p> Conclusion <p>Our findings provide strong evidence that Plumbagin significantly reduced neuroinflammation, provided neuroprotective support, and alleviates cognitive impairment, as demonstrated through <i>in-silico</i> and <i>in-vivo</i> analyses.</p>

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Plumbagin Ameliorate 5-Fluorouracil-Induced Cognitive Impairment in Adult Zebrafish: In-silico and In-vivo Evidences

  • 期刊论文

  • 发表日期：

    2026年1月26日

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  • Sonima Prasad,
  • Biplob Sarkar,
  • Kaunava Roy Chowdhury,
  • Ankit Rathee,
  • Charan Singh,
  • Arti Singh

摘要

Background

Chemotherapy is a crucial part of cancer treatment, but it has been linked to a set of cognitive impairments. 5-Fluorouracil, a chemotherapeutic drug causing mitochondrial dysfunction and neurodegeneration. This study primarily aimed to evaluate the effect of Plumbagin on mitochondrial dynamics, neuroinflammation and oxidative stress in adult zebrafish subjected to 5-Fluorouracil-induced cognitive impairment.

Material and Methods

In this study, initially in-silico studies were conducted for lead compound identification. For the in-vivo studies, adult zebrafish (~ 6–8 months old; 470–530 mg; 126 animals are used) were randomly assigned to 7 groups and treated with 5-Fluorouracil (25 mg/kg; i.p.) for 1 day followed by post-treated with Plumbagin (10 and 20 mg/kg; i.p.) and Donepezil (5 mg/kg; i.p.) for 6 days. Behavioral, biochemical, molecular, mitochondrial, and histopathological analyses were performed after completion of the study.

Result

In-silico analyses revealed that Plumbagin exhibits stronger binding affinity as compared to 5-Fluorouracil. In vivo findings further demonstrated that post-treatment with Plumbagin significantly mitigates oxidative stress markers, reduces neuroinflammatory cytokines, and enhances mitochondrial functioning (mitochondrial enzyme complexes, caspases-3, and cellular viability) relative to zebrafish treated with 5-Flurouracil alone. Additionally, Plumbagin treatment led to marked reduction in GSK-3β expression, improvements in mitochondrial structure (as observed through Transmission electron microscopy analysis. Further, post-treatment with Plumbagin significantly improved mitochondrial morphology (as observed through TEM analysis) and neuronal morphology (assessed via Hematoxylin and Eosin staining and Nissl staining) as compared to 5-Fluorouracil -treated zebrafish.

Conclusion

Our findings provide strong evidence that Plumbagin significantly reduced neuroinflammation, provided neuroprotective support, and alleviates cognitive impairment, as demonstrated through in-silico and in-vivo analyses.