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. 2025 Mar:107:22-36.
doi: 10.1016/j.neuro.2025.01.003. Epub 2025 Jan 22.

In silico and In vivo protective effect of biochanin-A mitigating doxorubicin- induced cognitive deficits and neuroinflammation: Insights to the role of p-Tau and miR-132

Sarah A Hussein  1 , Mai F Tolba  2 , Haidy E Michel  3 , Amgad Albohy  4 , Samar S Azab  5
Affiliations

In silico and In vivo protective effect of biochanin-A mitigating doxorubicin- induced cognitive deficits and neuroinflammation: Insights to the role of p-Tau and miR-132

Sarah A Hussein et al. Neurotoxicology. 2025 Mar.

Abstract

Doxorubicin (DOX)-induced chemobrain has been reported in several studies. Its main culprit is the induction of massive amounts of reactive oxygen species (ROS), hence triggering damage to brain tissues and thus leading to neuroinflammation. Biochanin A (BIO-A) is known to be an antioxidant, anti-inflammatory, and neuroprotective agent. An in silico study was designed to examine the potential neuroprotective effect of BIO-A. An in vivo study was used to evaluate the modulatory effect of BIO-A on cognitive impairment engendered by DOX. The insilico investigation proved the putative neuroprotective effect of BIO-A. In the in vivo study, BIO-A treatment counteracted DOX-induced memory deficits, as evidenced by improved spatial memory in rats compared to the DOX-only group. BIO-A also reversed DOX-triggered hippocampal neurodegeneration and neuroinflammation, supported by a significant decrease in tissue contents of NF-κB (p65) by 32 % and NLRP3 by 36 % versus the DOX-only group. BIO-A also abrogated DOX-induced neurodegneration, as evidenced by increasing SIRT1 content by 2-fold and BDNF content by 2-fold versus the DOX-only group in hippocampal tissues. In addition, BIO-A ameliorated DOX-augmented apoptosis in the hippocampus, as evidenced by lowering caspase-3 content in the hippocampus by 26 % versus the DOX-only group. Regarding tauopathy, BIO-A reversed DOX-increased tauopathy by 35 % versus the DOX-only group. The neuroprotectant miR-132 was increased by BIO-A in hippocampal tissues by 4-fold, contrary to the DOX-only group. Thus, BIO-A treatment modulated DOX-induced behavioral, histological, and molecular changes in the hippocampi of rats. Further studies are recommended to evaluate BIO-A in early clinical trials for the purpose of protection against chemobrain in cancer patients.

Keywords: BIO-A; Chemobrain; DOX; MiR-132; SIRT1; Tauopathy.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper.

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