Licoricidin improves neurological dysfunction after traumatic brain injury in mice via regulating FoxO3/Wnt/β-catenin pathway

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability around the world with no effective treatments currently. The present study was aimed to investigate the neuroprotective effect of licoricidin, one of the major components of licorice extract, on TBI mice and further explore the underlying mechanism. Male C57BL/6 mice were modeled by a modified weight-drop method to mimic TBI. All animals received treatment 30 min after TBI. The modified Neurological Severity Score (NSS) tests were performed at 2 h and 1-3 days after TBI. The brain edema was analyzed by dry-wet weight method. The malonaldehyde (MDA) levels and the activities of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) were determined by Elisa. Apoptotic neurons were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunofluorescence and the expression of apoptotic proteins were measured by western blot. Activation of the FoxO3/Wnt/β-catenin was evaluated by western blot. The results showed that treatment with licoricidin could significantly decline the NSS scores and reduce the brain edema, hence promote the recovery of neurological function in TBI mice. It also elevated the phosphorylation of p66^shc, brought down the levels of MDA, as well as antagonized the decrement in activities of GSH-PX, SOD and CAT induced by TBI. Moreover, licoricidin decreased the TUNEL positive neurons, downregulated the expression of Cyt-C, cleaved-Caspase-3, cleaved-Caspase-9 and Bax and upregulated the Bcl-2, attenuated cellular apoptosis. Licoricidin decreased the expression of FoxO3 and increased the Wnt/β-catenin in TBI mice. In conclusion, Licoricidin exerted neuroprotective effect on TBI model and the effect was possibly due to its antioxidative effect and antiapoptotic effect via regulating the FoxO3/Wnt/β-catenin pathway. Licoricidin may be a candidate drug for TBI therapy.

Keywords: Apoptosis; FoxO3/Wnt/β-catenin pathway; Licoricidin; Oxidative stress; Traumatic brain injury.