To explore the antidepressant effect and its mechanism of effective components of Lilium brownii based on brain-derived neurotrophic factor/protein kinase B/mammalian target of rapamycin (BDNF/AKT/mTOR) pathway.

In cellular experiments, the experiments were divided into control group (cell culture solution), model group (corticosterone 400 μmol·L^-1), lily saponin low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy saponin), lily saponin high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy saponin), lily polysaccharide low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy polysaccharide), and lily polysaccharide high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy polysaccharide). Except for the blank group, the remaining groups were modeled with corticosterone to establish human neuroblastoma cells (SH-SY5Y) injury, and cell survival was detected. In the animal experiments, 48 male ICR mice were randomly divided into 6 groups: model group (drinking water with the same amount), low dose of lily saponin (50 mg·kg^-1), high dose of lily saponin (100 mg·kg^-1), low dose of lily polysaccharide (50 mg·kg^-1), high dose of lily polysaccharide (100 mg·kg^-1) and positive drug control group (fluoxetine,10 mg·kg^-1). Each group was given acute stress modeling in mice, and changes in behavioral indexes were observed. Serum corticosterone levels were measured by enzyme-linked immunosorbent assay. The relative expression levels of proteins such as postsynaptic densifier 95 (PSD95) and synapsin in the prefrontal cortex of mice were detected by protein immunoblot analysis.

In the cellular experiments, the cell survival rates of each subgroup were (71.46±1.92)%, (95.97±1.11)%, (105.51±1.80)%, (107.48±0.27)% and (107.66±3.61)%, respectively. The differences between the administered groups and the model group were all statistically significant (all P<0.01). In the animal experiments, the cumulative immobilization time of mice with suspended tails in model group, low and high dose of lily saponin groups, low and high dose of lily polysaccharide group and positive drug group was (122.75±4.77), (90.75±2.09), (66.13±3.23), (79.75±2.84), (54.38±4.40), and (42.00±6.34) s, respectively; the levels of corticosterone in the serum of mice were (236.94±6.17), (213.88±3.95), (165.52±2.19), (203.40±3.27), (170.18±2.18) and (104.96±3.87) ng·mL^-1, respectively; the relative expression levels of brain-derived neurotrophic factor (BDNF) were 0.26±0.03, 0.74±0.25, 0.86±0.03, 0.97±0.11, 0.92±0.13 and 1.05±0.23, respectively; the relative expression levels of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) were 0.26±0.03, 0.60±0.19, 0.75±0.09, 0.82±0.05, 0.94±0.23 and 0.58±0.07, respectively; the relative expression levels of phosphorylated mammalian target of rapamycin/mammalian target of rapamycin protein (p-mTOR/mTOR) were 0.46±0.04, 0.52±0.19, 0.60±0.18, 1.01±0.01, 0.98±0.06 and 0.93±0.10, respectively; the relative expression levels of postsynaptic density protein-95 (PSD95) were 0.36±0.05, 0.50±0.08, 0.60±0.09, 0.73±0.09, 0.84±0.18 and 1.00±0.12, respectively; the relative expression levels of synapsin protein were 0.13±0.04, 1.03±0.02, 1.16±0.06, 1.02±0.00, 1.00±0.04 and 0.65±0.15, respectively. Except the p-mTOR/mTOR and PSD95 in high dose of lily saponin, the differences of the above indexes between the model group and the high dose groups were all statistically significant (P<0.05, P<0.01).

Lily saponins and polysaccharides may improve synaptic plasticity in prefrontal cortex by modulating the BDNF/AKT/mTOR signaling pathway, which improves depressive-like behavior and suppresses serum corticosterone levels in behavioral despair mice. Among them, lily polysaccharides were slightly better than lily saponins in improving synaptic plasticity.