Front Pharmacol:栀子豉汤通过调节GSH/GSSG途径减轻氧化应激损伤逆转CUMS大鼠抑郁行为

2022-06-05 紫菀款冬 MedSci原创

从细胞和动物水平验证栀子豉汤抗抑郁作用中谷胱甘肽途径的抗氧化作用。

背景:抑郁症是导致残疾和丧失工作能力的主要疾病之一。目前常规药物治疗具有抗药性、药物疗效延迟和严重的副作用等缺陷,影响患者的预后。因此,在寻找新的抗抑郁药时,必须考虑疗效和可接受性,而中医药已成为一个潜在的探索领域。

栀子豉汤(ZZCD)首载于《伤寒论》,在中国被广泛用于治疗抑郁症、发热性疾病和失眠症已有1000多年的历史。目前关于ZZCD抗抑郁机制及药效物质基础的研究尚未见报道。前期研究发现,ZZCD可以减轻谷氨酸诱导的PC12细胞氧化应激损伤,从而发挥神经保护作用,并且ZZCD的抗抑郁作用已在CUMS大鼠模型中得到验证。

目的:从细胞和动物水平验证ZZCD抗抑郁作用中谷胱甘肽途径的抗氧化作用。

方法:采用慢性不可预测轻度刺激结合单纯喂养建立抑郁动物模型蔗糖偏好试验、强迫游泳试验、尾部悬挂试验观察大鼠行为。采用基于超高效液相色谱-四极杆/飞行时间质量的代谢组学方法分析抑郁大鼠的脑代谢谱。并检测大鼠脑内GSH、GSSG、ROS、SOD、GR、GPx等与氧化应激相关的代谢产物。

结果:CUMS可降低大鼠蔗糖偏好、增加强迫游泳试验的不动时间,ZZCD治疗可逆转这种趋势。筛选并分析出26种与ZZCD抗抑郁药相关的差异代谢产物和7条代谢途径,包括苯丙氨酸、酪氨酸和色氨酸生物合成、谷胱甘肽代谢、苯丙氨酸代谢、赖氨酸降解、半胱氨酸和蛋氨酸代谢、酪氨酸代谢和色氨酸代谢。CUMS升高大鼠脑组织中ROS、GSSG水平,降低GSH水平以及GR、GPx和SOD活性,而ZZCD能显著上调GR、GPx和SOD的活性及GSH水平,降低ROS、GSSG水平

结论:栀子豉汤具有潜在的抗抑郁作用,其机制与逆转抑郁大鼠脑内谷胱甘肽失衡和氧化应激有关。

文献来源:

Zhang Y, Fang YC, Cui LX, et al. Zhi-Zi-Chi Decoction Reverses Depressive Behaviors in CUMS Rats by Reducing Oxidative Stress Injury Via Regulating GSH/GSSG Pathway. Front Pharmacol. 2022; 13: 887890. https://doi.org/10.3389/fphar.2022.887890

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    2022-10-22 yb6560
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    2022-06-05 ms8000001137235674

    栀子豉汤治热郁胸膈,凉膈散治热扰胸膈。

    0

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