The Study On Neuroprotection Effect Of Glycyrrhizic Acid

Numerous studies report that herbal preparations and their natural compoundsdisplay broad protective effects against neurotoxicity in various neurodegenerativediseases. Glycyrrhiza Radix, one of the Chinese traditional crude drugs, showsvarious pharmacological activities including anti-inflammatory, anti-obesity,anti-virus and anti-oxidative effects.It is well evidenced that GA shows remarkableneuro-protective effects against6-hydroxydopamine or glutamate-induced damage inneuronal cells.Glycyrrhizic acid (GA), a major compound separated form GlycyrrhizaRadix, possesses anti-inflammatory and anti-viruses effects. Previous studydemonstrated that GA displays neuro-protective effect against6-hydroxydopamine-induced PC12cell death via PI3K/AKT pathway. The protectiveeffect of GA was also confirmed in rat primary neurons and hippocampal slices.Our present study focuses on the neuro-protective effect of glycyrrhizic acid (amajor compound separated from Glycyrrhiza Radix) against glutamate-inducedcyto-toxicity in differentiated PC12(DPC12) cells. Results revealed that GAtreatment strikingly improved cell viability and ameliorated mitochondrial abnormalalteration caused by glutamate in DPC12cells. GA reversed glutamate-suppressedB-cell lymphoma2(Bcl-2) level, inhibited glutamate-enhanced expressions of Baxand Cleaved Caspase3, and reduced Cytochrome C (Cyto C) release. Exposure toglutamate strongly inhibited the phosphorylation of AKT and extracellularsignal-regulated kinases (ERKs); however, GA pretreatment only enhanced theactivation of ERKs but not AKT. The presence of PD98059(a MEK inhibitor) but notLY294002(a PI3K inhibitor) diminished the potency of GA in improving the viabilityof glutamate-exposed DPC12cells. All these results indicate that ERKs andmitochondria related pathways are essential for the neuro-protective effect of GA against glutamate-induce toxicity in DPC12cells.In the present study, the effect of GA against methyl-4-phenylpyridine ion(MPP+)-induced differentiated PC12(DPC12) cells damage was investigated.Compared with MPP+-treated cells, GA strongly improved cell viability, restoredmitochondrial dysfunction, suppressed the over-expression of cleaved PARP, reducedLDH over-release and intracellular Ca2+overload. The protective effect of GA on cellsurvival was further confirmed in primary cortical neurons. Additionally, GA stronglyincreased the expressions of phosphorylated extracellular signal-regulated kinase(P-ERKs) and its migration from cytoplasm to nucleus. PD98059, an inhibitor ofERKs, blocked GA-enhanced ERKs activation and cell viability. However, GApretreatment showed no effects on the expressions of phosphor-AKT and total-AKT.These results indicate that GA-mediated neuro-protection is related to its modulationof multiple anti-apoptotic and pro-apoptotic factors especially ERKs signalingpathway.The study provides evidence supporting GA as a potential therapeutic agent usedfor the treatment of neurodegenerative diseases and neural injury.