Barbaloin Attenuates Cisplatin‐Induced Hippocampal Neurotoxicity by Suppressing Oxidative Stress, Neuroinflammation, and Apoptosis: In Vivo and In Silico Evidence

ABSTRACT

The neurotoxicity of cisplatin (CIS) in the hippocampal leads to cognitive effects caused by oxidative stress, neuroinflammation, apoptosis, and dysfunction of neurotransmitters. The major bioactive phytonutrient in Aloe vera is barbaloin (BLN), which has been shown to have antioxidant and anti‐inflammatory effects, but its neuroprotective ability against CIS‐induced neurotoxicity has not been investigated. To assess the neuroprotective action of BLN in CIS‐induced hippocampal neurotoxicity in rats and to understand the molecular interactions between BLN and major neuroinflammatory and apoptotic proteins. A total of 24 male Wistar rats were split into 4 groups ( n  = 6): control, CIS (5 mg/kg), CIS + BLN 25 mg/kg, and CIS + BLN 50 mg/kg over 21 days. Cognitive ability (Morris water maze), oxidative stress indicators (MDA, GSH, SOD, CAT), neuroinflammatory cytokines (TNF‐α, IL‐1β, IL‐6, NF‐κB, TGF‐β1), caspase‐3, neurotransmitters, and hippocampal histopathology were measured. Molecular docking and 100‐ns molecular dynamics simulations (MDS) with MM‐GBSA analysis were done with TNF‐α, TGF‐β1, NF‐κBp65, and caspase‐3. BLN significantly reduced cognitive impairment, oxidative stress, neuroinflammation, and apoptosis, and restored neurotransmitter homeostasis and hippocampal cytoarchitecture (all p  < 0.0001). Molecular docking demonstrated positive binding energies (− 7.226 to −8.566 kcal/mol), and MDS revealed the presence of stable BLN–protein complexes (Δ G _bind  = −56.07 kcal/mol for TGF‐β1). BLN exhibits considerable neuroprotective properties against CIS‐induced neurotoxicity in the hippocampus, suggesting its potential as a natural dietary phytonutrient supplement to ameliorate chemotherapy‐induced cognitive impairment.