Honokiol, a neuroprotectant against mouse cerebral ischaemia, mediated by preserving Na+, K+-ATPase activity and mitochondrial functions

Honokiol, a component of the herb Magnolia offzcinalis, exhibits antioxidant, anti-inflammatory and anxiolytic properties, increases seizure threshold, and promotes neurite outgrowth. Because stroke has become the second leading cause of death in industrialized countries, an effective neuroprotectant is urgently required. In this study, we attempted to elucidate in a mouse cerebral ischaemia model whether honokiol could be a neuroprotectant. Adult male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion for 45 min. Honokiol (10 mu g/kg in 0.2 ml of saline) or control vehicle was intraperitoneally administered twice, 15 min. before and 60 min. after the induction of ischaemia. Cerebral ischaemia induced by this method was associated with an increase in synaptosomal production of reactive oxygen species, with decreases in synaptosomal mitochondrial membrane potential (Delta Psi m) and synaptosomal mitochondrial metabolic function, and with reductions in Na+, K+-ATPase activities of tissues isolated from selected brain regions. Administration of honokiol resulted in significant reductions in brain infarct volume and in synaptosomal production of reactive oxygen species. The decreases in synaptosomal mitochondrial membrane potential, synaptosomal mitochondrial metabolic function and tissue Na+, K+-ATPase activities observed in the ischaemic brains were also attenuated by honokiol treatments. It is concluded that honokiol can protect brain against ischaemic reperfusion injury and preserve mitochondrial function from oxidative stress. Regarding therapeutic application, further studies are needed to assess the efficacy and safety of honokiol in clinical situations.