Effects Of Extractive And Active Constituents Of Glycyrrhiza Uralensis Fisch On ?-synuclein Aggregation

?-synuclein, a neuronal protein ample in the brain, not only played an important role in the maintenance of synaptic function properly, but also closely related to a series of neurodegenerative diseases, especially to Parkinson's disease(PD). Aggregated ?-synuclein is the major component of inclusions in PD patients' brain, and has been revealed to have cytotoxic effect for nerve cells. Thus the inhibition of ?-synuclein aggregation process has been generally accepted as a considerable prevention or treatment strategy for PD. Glycyrrhiza uralensis Fisch is a kind of traditional herbal medicine in china, which is known to have anti-oxidation, anti-inflammation and anti-cancer properties. Triterpene and flavonoids were found to be the major pharmacological active ingredients in Glycyrrhiza uralensis, including isoliquiritigenin(ILG), liquiritin(LT), glycyrrhetinic acid(GRA), liquiritigenin(LG), glycyrrhizic acid(GA). Here, we investigated the effect of extractive and active constituent of Glycyrrhiza uralensis on the aggregation of ?-synuclein both in vitro and in a transgenic Caenorhabditis elegans PD model. In vitro, ILG, LT and Glycyrrhiza uralensis extract(GUE) inhibited the amyloid formation of ?-synuclein; moreover, ILG could disaggregate preformed mature fibril and alleviate the membrane damage caused by the aggregated ?-synuclein. Circular dichroism spectroscopy results suggested LT and GUE could delay the secondary structural transformation of ?-synuclein from unstructured coils to ?-sheets, while ILG showed no such inhibition effect. In vivo, ILG, LT, GRA and GUE could reduce the formation of fibril in C.elegans NL5901. Moreover, ILG, LT and GUE could extended the life span of NL5901. Together, the data suggested that ILG and LT may be further considered as drug candidate for PD treatment.