18α￣glycyrrhetinic acid promoting neural stem cells proliferation through antioxidant in the subventricular zone of adult mice / 解剖学报

ABSTRACT

Objective To explore the effect of 18α-glycyrrhetinic acid (18α-GA) on the proliferation of adult mice neural stem cells (NSCs) and its underlying mechanism. Methods One hundred 6-month BALB/c mice were randomly divided into DMSO control group and 18α-GA group (mice were intraperitoneally injected with 40 mg/kg 18α-GA every day for 2 months). The proliferation capability, oxidative status and nuclear factor E2-related factor 2 (Nrf2) level of NSCs in the adult mice subventricular zone (SVZ) were measured through both in vivo and in vitro experiments, including Ki-67 staining, neurosphere formation assay, BrdU incorporation, CCK-8 assay, reactive oxygen species (ROS) detection, superoxide dismutase 1 (SOD1) determination, Real-time PCR and Western blotting. Results Elevated Ki-67 positive cells were observed in SVZ of mice with 18α-GA application. Meanwhile, ROS level attenuated but SOD1 mRNA and protein level increased significantly in the SVZ of 18α-GA group mice, the latter of which were (3. 17 ± 0. 073) and (2. 12±0. 02) times respectively than that of the control group (P<0. 05 and P<0. 001). Likewise, the similar changes were exhibited in vitro data. NSCs of 18α-GA group mice displayed higher proliferation potency confirmed by accelerated neurosphere formation and increased neurosphere number (P<0. 001), as well as higher BrdU positive ratio (P<0. 01) and NSCs vitality (P<0. 001). NSCs of mice with 18α-GA injection exhibited decreased ROS level by 18. 91%±4. 33% (P<0. 05) and enhanced SOD1 level, compared with those in NSCs of DMSO group mice. Furtherly, the Nrf2 expression in SVZ and NSCs of 18α-GA group mice was higher than that of the control group. Conclution 18α-GA administration plays a vital role in the maintainence and amelioration of adult mice NSCs proliferation through activating SOD1 and diminishing ROS aggregations.