Protective effect of Rosemarinus officinalis and its nanoparticles against chemobrain and neuroinflammation in rats: Involvement of Wnt/β-Catenin signaling and apoptotic machineries

Abstract

Chemobrain, constitutes a major debilitating effect experienced by cancer patients receiving chemotherapy as oxaliplatin that induces chemofog and neuroinflammation. This study aimed to evaluate the protective effect of the ethanol extract of the edible Rosemarinus officinalis aerial parts against chemobrain and neuroinflammation in rats. Metabolic profiling of Rosmarinus officinalis L. aerial parts ethanol extract by LC-qTOF-MS/MS revealed 16 compounds belonging to phenolic diterpenes, triterpenes and monoterpenes.Its prepared nanoemulsion revealed suitable polydispersity, nanometer particle size and negatively charged surface both in freshly prepared state and after storage. Cognitive impairment and neuroinflammation was induced in rats using oxaliplatin. Male rats were allocated in five groups as follows: Group 1 (control group); Groups 2, 3, 4, and 5 received oxaliplatin (4 mg/kg, i.p) twice a week for four weeks. Groups 3 and 4 received a daily oral dose of Rosmarinus officinalis at doses of 50 and 100 mg/kg, respectively, for four successive weeks. Group 5 received a daily intranasal dose of Rosmarinus officinalis nanoemulsion at a dose of 1 mg/kg. Behavioral, histological and biochemical parameters were determined to evaluate the cognitive function in rats. Rosmarinus officinalis extracts and nanoemulsion administration halted the destruction of hippocampal normal structure and memory decline provoked by oxaliplatin injection. They hindered oxaliplatin effect on antioxidant enzymes such as catalase and reduced glutathione. Rosmarinus officinalis treatment activated Wnt/β-catenin axis, ameliorated neuroinflammation and apoptotic markers; caspase-3 and p53 with no effect on the anticancer activity of oxaliplatin. This highlighted the promising neuroprotective potential of Rosmarinus officinalis in chemofog that further consolidates its folk medicinal popularity.