To explore the potential molecular mechanism by which saffron exerts its antidepressant effect by regulating the expression of angiotensinogen (Agt) in the nucleus accumbens (NAc) and regulating synaptic remodeling.
Fifty mice were randomly divided into five groups: blank control group, model group, fluoxetine group, low-dose saffron group, and high-dose saffron group. The chronic unpredictable stress (CUMS) model was established in mice (except the blank control group), and continuous intragastric administration was performed for 7 days after modeling.. Depressive-like behaviors of mice were evaluated using the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST). The mRNA and protein expression levels of Agt in the NAc were detected. The mRNA levels of angiotensin II (Ang-Ⅱ), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in mouse brain tissues were measured. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in mouse brain tissues were assayed. Additionally, the protein expression levels of synaptophysin (Syp), postsynaptic density protein 95 (Psd-95), and brain-derived neurotrophic factor (Bdnf) in mouse brain tissues were determined.
Compared with the model group, the fluoxetine group, low-dose saffron group, and high-dose saffron group showed improved depressive-like behaviors, with a significant increase in SPT and a significant decrease in immobility time in FST and TST (P<0.05). Compared with the model group, the high-dose saffron group exhibited significantly reduced mRNA levels of Agt, Ang-Ⅱ, IL-6, and TNF-α (P<0.05), decreased MDA content, and significantly increased SOD activity in brain tissues (P<0.05). The protein expression of Syp, Psd-95, and Bdnf in brain tissues was significantly upregulated in the high-dose saffron group (P<0.05).
Crocetin exerts its antidepressant effect by inhibiting the expression of Agt in the NAc, regulating the renin-angiotensin system (RAS), alleviating neuroinflammation and oxidative stress, and promoting synaptic remodeling mediated by Syp, Psd-95, and Bdnf.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |