Licorice extract and carbenoxolone protect PC12 cells against serum/glucose deprivation-induced apoptosis through modulation of caspase-3 and PARP activation.

Objective: Serum/glucose deprivation in cultured PC12 cells is considered an appropriate model for investigating detailed mechanisms of ischemia-induced brain injury. Here, we aimed to study the anti-apoptotic effects of licorice (Glycyrrhiza glabra L.) root extract and carbenoxolone on PC12 cells cultured in the serum/glucose deprivation (SGD) condition.

Materials and methods: Cells were incubated with the different concentrations of the G. glabra methanol extract (5-320 µg/ml) and carbenoxolone (0.5-32 µM) for 2 hr before being deprived of serum/glucose. Protection against cytotoxicity, increase in reactive oxygen species (ROS), and apoptosis was analyzed with resazurin, dichlorofluorescein diacetate (DCFH-DA), and western blot, respectively.

Results: Serum/glucose deprivation induced cell death and apoptosis in PC12 cells. Pretreatment with the G. glabra methanol extract at 5-20 µg/ml and carbenoxolone at 0.5-2 µM for 2 hr significantly decreased the cytotoxicity (p<0.05), and pretreatment with the G. glabra methanol extract (5-160 µg/ml) and carbenoxolone (0.5 μM) significantly decreased the ROS content. Pretreatment with the G. glabra methanol extract and carbenoxolone at 5-20 µg/ml significantly prevented from the Poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage.

Conclusion: Taken together, this study confirms the protective and free radical-scavenging potency of licorice extract and carbenoxolone in in vitro model of ischemia. Overall, it seems that pretreatment with the licorice extract and carbenoxolone may potentially slow the progression of brain ischemia.