Glycyrrhizin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

초록

Glycyrrhizin (GL), a triterpene present in the roots and rhizomes of licorice, Glycyrrhiza glabra, has been shown to have anti-inflammatory and anti-viral effects. In a previous report, we showed neuroprotective effects of GL in the postischemic rat brain after middle cerebral artery occlusion (MCAO). This neuroprotective effect was accompanied by improvements in motor impairment and neurological deficits and suppressions of microglia activation and proinflammatory cytokine induction. Interestingly, GL almost completely blocked HMGB1 secretion in the postischemic brain and in lipopolysaccharide (LPS)-treated microglia cells. In the present study, the authors investigated whether GL has a beneficial effect on KA-induced neuronal cell death. An intracerebroventricular (i.c.v.) injection of 0.94 nmole (0.2 μg) of KA produced typical neuronal cell death both in CA1 and CA3 regions of the hippocampus. Although, there was no significant difference in the time course or severity of epileptic behavior, the systemic administration of GL at 30 min before KA administration significantly attenuated this neuronal cell death. GL was found to suppress neuronal cell loss when injected at 10 mg/kg and the effect was enhanced at 50 mg/kg. Furthermore, this GL-mediated neuroprotection was accompanied by marked suppression of gliosis and proinflammatory marker (COX-2, IL-1β, and TNF-α) inductions. It is interesting to note here that GL treatment suppressed HMGB1 release in KA-treated mouse, resulting in significant decrease of HMGB1 levels in serum and cerebrospinal fluid, which might explain its anti-inflammatory effect. Together these results indicate that GL has neuroprotective efficacy in the KA-injected mouse brain via its anti-inflammatory, which is conferred, at least in part, by inhibiting HMGB1 secretion.