This study aims to investigate whether Xiaoxianxiong Decoction (XXXD) can exert a protective effect in atherosclerosis (AS) by activating growth arrest specific 6 (GAS6)/receptor tyrosine kinase AXL (AXL) and inhibiting endothelial cell ferroptosis. This experiment was approved by the Animal Experiment Ethics Committee of Shaanxi Academy of Traditional Chinese Medicine (approval number: 2022-10). At the animal level, the apolipoprotein E knockout (ApoE-/-) mice were fed with a high-fat diet (HFD) to establish the AS model. At the cellular level, the endothelial cell injury model was established with oxidized low-density lipoprotein (ox-LDL), and the cell viability, lactate dehydrogenase (LDH), reactive oxygen species (ROS), Fe2+, and lipid peroxidation indicators malondialdehyde (MDA), superoxide dismutase (SOD), total glutathione peroxidase (GPx), and glutathione reductase (GR) were detected. Western blot was used to detect the expression of GAS6, AXL, glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) proteins. The results showed that XXXD could reduce body weight, aortic plaque area and lipid accumulation in AS mice, improve dyslipidemia, increase lipid antioxidant capacity in aorta and endothelial cells (increase SOD, GPx and GR, inhibit MDA), reduce LDH, ROS, MDA and Fe2+ levels in endothelial cells, and up-regulate the expression of GAS6, AXL, GPX4, and SLC7A11 proteins to improve AS and endothelial cell injury. The above results confirmed that XXXD can alleviate AS by regulating ferroptosis of endothelial cells through the GAS6/AXL signaling pathway.
| 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 |