Neuroprotective effects of osthole pretreatment against traumatic brain injury in rats

Osthole, a coumarin compound isolated from the plant-derived herb Cnidium monnieri, has been the subject of considerable interest because of its broad spectrum of pharmacological properties. The aim of this study was to investigate the potential protective effects of osthole in adult rats in the setting of traumatic brain injury (TBI). We employed Feeney's weight-drop model to ascertain whether intraperitoneal administration of osthole (10 mg/kg, 20 mg/kg and 40 mg/kg) 30 min before TBI could reduce the severity of neurological deficits, cerebral edema, and hippocampal neuron loss. The levels of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD), the expressions of Bcl-2, Bax, and active caspase-3, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were also measured to characterize the antioxidative and antiapoptotic properties. A significant reduction of neurological deficits, cerebral edema and hippocampal neuron loss was observed in the osthole pretreatment groups (20 mg/kg and 40 mg/kg, but not 10 mg/kg) by 24 h after TBI compared with the TBI group. Furthermore, pretreatment with osthole (40 mg/kg) significantly increased the activity of SOD, the level of GSH, and the ratio of Bcl-2/Bax, and also reduced the level of MDA, the expression of active caspase-3, and the number of apoptotic cells at 24 h after TBI. In summary, these results suggested that osthole had a neuroprotective effect against TBI, and the protection may be associated with its antioxidative and antiapoptotic functions.

► We investigated the neuroprotective effects of osthole against TBI in rats.
► Osthole alleviated neurological deficit, cerebral edema and hippocampal neuron loss.
► Osthole reduced the level of oxidative stress.
► Osthole reduced active caspase-3 expression and increased the ratio of Bcl-2/Bax.