The therapeutic potential of glycyrrhizic acid and its metabolites in neurodegenerative diseases: Evidence from animal models

Neurodegenerative diseases, mostly occurring in the elderly population, are the significant cause of disability and death worldwide. The pathogenesis of neurodegenerative diseases is still largely unknown yet, although they have been continuously explored. Thus, there is still a lack of safe, effective, and low side effect drugs in clinical practice for the treatment of neurodegenerative diseases. Pieces of accumulating evidence have demonstrated that licorice played neuroprotective roles in various neurodegenerative diseases. In the past two decades, increasing studies have indicated that glycyrrhizic acid (GL), the main active ingredient from traditional Chinese medicine licorice (widely used in the food industry) and a triterpenoid saponin with multiple pharmacological effects (such as anti-oxidant, anti-inflammatory, and immune regulation), and its metabolites (glycyrrhetinic acid and carbenoxolone) play a neuroprotective role in a range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy. This review will elaborate on the multiple neuroprotective mechanisms of GL and its metabolites in this series of diseases, aiming to provide a basis for further research on these protective drugs for neurodegenerative diseases and their clinical application. In summary, GL may be a promising candidate drug for the therapy of neurodegenerative diseases.