Protective effect of <i>Rosmarinus officinalis</i> and its nanoparticles against chemobrain and neuroinflammation in rats: involvement of Wnt/β-catenin signaling and apoptotic machineries

Chemobrain is a major debilitating effect on cancer patients receiving oxaliplatin for chemotherapy. This study aimed to evaluate the protective effect of the ethanol extract of the edible aerial parts of <i>Rosmarinus officinalis</i> against chemobrain and neuroinflammation in rats. The metabolic profiling of the ethanol extract of the <i>Rosmarinus officinalis</i> L. aerial parts was performed by LC-qTOF-MS/MS, and 16 compounds belonging to phenolic diterpenes, triterpenes and monoterpenes were revealed. The prepared <i>Rosmarinus officinalis</i> L. nanoemulsion revealed optimal polydispersity, nanoscale particle size, and a negatively charged surface in both freshly prepared and after storage states. Cognitive impairment and neuroinflammation were induced in rats using oxaliplatin. Male rats were allocated into five groups: group 1 was the vehicle reference group and groups 2, 3, 4, and 5 received oxaliplatin (4 mg kg^-1, i.p.) twice a week for four weeks. Groups 3 and 4 received a daily oral dose of <i>Rosmarinus officinalis</i> at 50 and 100 mg kg^-1, respectively, for four successive weeks. Group 5 received a daily intranasal dose of <i>Rosmarinus officinalis</i> nanoemulsion of 1 mg kg^-1. Behavioral, histological and biochemical parameters were determined to evaluate the cognitive function in rats. <i>Rosmarinus officinalis</i> extracts and the administered nanoemulsion halted the destruction of hippocampal normal structure and memory decline, triggered by the oxaliplatin injection. They hindered the effects of oxaliplatin on antioxidant markers, such as catalase and reduced glutathione. <i>Rosmarinus officinalis</i> treatment activated Wnt/β-catenin axis and ameliorated neuroinflammation and apoptotic markers, such as caspase-3 and p53, showing no effect on the anticancer activity of oxaliplatin. This highlighted the promising neuroprotective potential of <i>Rosmarinus officinalis</i> in chemofog, which further consolidated its folk medicinal popularity.