Glycyrrhizin inhibits the neurotoxic effects and mechanisms induced by morphine / 中国临床药理学与治疗学

ABSTRACT

AIM:To investigate the regulatory ef-fects and mechanisms of glycyrrhizin on morphine-induced neurotoxicity.METHODS:A neurotoxicity model was established by intracerebroventricular injection of morphine.Glycyrrhizin was adminis-tered intraperitoneally for 5 and 10 days.Pathologi-cal observation,protein immunoblotting,cell viabil-ity,apoptosis,and primary neuron differentiation were assessed.RESULTS:After morphine treat-ment,neuronal loss,decreased cell viability,in-creased apoptosis,axonal breakage,and cell shrink-age were observed in cortical tissue.Glycyrrhizin administration significantly improved cell viability,and axonal,dendritic,and cell body structures gradually became intact,with reduced apoptosis.The phosphorylation levels of protein Akt at posi-tion 473 and PKA at position 197 decreased,while autophagy-related proteins Beclin and LC3B1/2 re-mained unchanged.CONCLUSION:Glycyrrhizin sig-nificantly inhibits morphine-induced neuronal dif-ferentiation suppression and neuronal apoptosis,which may be mediated through the synergistic ef-fects of glycyrrhizin and morphine on the Akt path-way.