天麻素
细胞凋亡
半胱氨酸蛋白酶3
半胱氨酸蛋白酶
医学
神经科学
药理学
心理学
程序性细胞死亡
化学
生物化学
色谱法
作者
Hongyan Pei,Heping Shen,Jinhao Bi,Zhongmei He,Liping Zhai
摘要
Abstract Aim We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation. Methods The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpredictable mouse stress (CUMS) model. Through open field, elevated plus maze, forced swimming, and tail suspension tests, the effects of GAS on the CUMS mice behaviors were examined, and the levels of neurotransmitters were detected. The histopathological changes were assayed by H&E and IHC staining, and the protein expressions were detected by Western blotting. Small molecule‐protein docking and molecular dynamics experiments were conducted to simulate the binding mode between GAS and Caspase‐3. Results Network pharmacological analysis revealed that Caspase‐3 was the action target of GAS. GAS could improve depression‐like behaviors in CUMS mice, elevate their neurotransmitter levels, ameliorate their nerve cell injury, and inhibit their Caspase‐3 expression. After knocking out Caspase‐3, the effects of GAS were inhibited. Molecular dynamics simulation and small molecule‐protein docking found that GAS bound to Caspase‐3 at SER25, inhibiting the maturation and activation of Caspase‐3. Conclusion We find that GAS can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis.
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