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Xiaoxianxiong Decoction alleviates atherosclerosis by activating GAS6/AXL to inhibit ferroptosis in endothelial cells
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Chen-xi LU1, 2, Ya-hui JIN2, Yuan LIU1, Fei-fei REN1, Xue WU2, *, Xia DU1, *
Acta Pharmaceutica Sinica | 2026, 61(5) : 1654 - 1662
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Acta Pharmaceutica Sinica | 2026, 61(5): 1654-1662
• Original Articles •
Xiaoxianxiong Decoction alleviates atherosclerosis by activating GAS6/AXL to inhibit ferroptosis in endothelial cells
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Chen-xi LU1, 2, Ya-hui JIN2, Yuan LIU1, Fei-fei REN1, Xue WU2, *, Xia DU1, *
Affiliations
  • 1Shaanxi Academy of Traditional Chinese Medicine, Xi'an 710003, China
  • 2Medical College of Yan'an University, Yan'an 716000, China
Published: 2026-05-12 doi: 10.16438/j.0513-4870.2025-1142
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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.

Xiaoxianxiong Decoction  /  atherosclerosis  /  endothelial injury  /  GAS6/AXL pathway  /  ferroptosis
陆晨曦, 靳雅惠, 刘园, 任菲菲, 吴雪, 杜霞. 小陷胸汤激活GAS6/AXL抑制内皮细胞铁死亡改善动脉粥样硬化. 药学学报, 2026 , 61 (5) : 1654 -1662 . DOI: 10.16438/j.0513-4870.2025-1142
Chen-xi LU, Ya-hui JIN, Yuan LIU, Fei-fei REN, Xue WU, Xia DU. Xiaoxianxiong Decoction alleviates atherosclerosis by activating GAS6/AXL to inhibit ferroptosis in endothelial cells[J]. Acta Pharmaceutica Sinica, 2026 , 61 (5) : 1654 -1662 . DOI: 10.16438/j.0513-4870.2025-1142
Year 2026 volume 61 Issue 5
220
105
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doi: 10.16438/j.0513-4870.2025-1142
  • Receive Date:2025-09-25
  • Online Date:2026-09-21
  • Published:2026-05-12
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  • Received:2025-09-25
  • Revised:2025-12-24
Affiliations
    1Shaanxi Academy of Traditional Chinese Medicine, Xi'an 710003, China
    2Medical College of Yan'an University, Yan'an 716000, China
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表12种不同金属材料的力学参数
科
Family
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Number of
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种数
Number of
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种数
Number of
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Percentage of total
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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
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