Nanostructured lipid‐loaded nerolidol ameliorate cyclophosphamide‐induced neuronflammation and cognitive dysfunction

Abstract Background Cyclophosphamide‐induced neurotoxic manifestations (neuronal oxidative stress, neuroinflammation, apoptosis and dementia) is major limitation for clinicians and reduce the quality of life of patients. However, to date, there are no approved adjuvant therapy available to attenuate these neurotoxic manifestations. Therefore, in the current study we explored the neuroprotective effect of nanostructured lipid loaded nerolidol nanoformulation, which is a naturally occurring lipophilic sesquiterpene having potent anti‐oxidant and anti‐inflammatory potential. Method Molecular docking study was performed to assertain the binding affinity of nerolidol with p65 subunit of NF‐kB. Nerolidol nanoformulation and nerolidol suspension were administered at the dose of 200 mg/kg, p.o for 14 days and neurotoxicity was induced in Swiss Albino mice by administrating a single dose of cyclophosphamide 200 mg/kg, i.p on 7 th day. Forced Swim test, step down latency and Passive Avoidance test were formed. On 15 th days animals were sacrificed, brain was removed and proceeded for the biochemical, histological and immunohistochemical study. Result Molecular docking study showed significant binding of nerolidol with NF‐kB. Neurobehavioural study showed significant cognitive derailment, biochemical study showed increased oxidative stress, nitrative stress and neuroinflammatory markers. Histopathological study revealed significant damage to CA1, CA2, CA3 regions of hippocampus and frontal cortex. Immunohistochemical study showed increased expression of p‐NF‐kB p65 and cleaved caspase‐3. These neurotoxic effects were reduced by administrating nerolidol nanoformulation at the dose of 200 mg/kg where as nerolidol suspension at the dose of 200 mg/kg was found to be ineffective. Conclusion The finding of the current study showed that cyclophosphamide induced significant neurotoxicity which was very well reversed by the nerolidol nanoformulation at the dose of 200 mg/kg. Nerolidol, thus, can be a future therapeutic molecule to counteract cyclophosphamide‐induced neuronal oxidative stress, neuroinflammation, apoptosis and dementia.