Wu Yang, Hao Ying, Yu Guohua, Li Li, Wang Shanglong, Li Xin, Zhang Zengliang, Zou Shengcan, Liu Zimin, Fan Pengcheng, Shi Yuanyuan
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, 10065, USA.
Heliyon. 2023 Feb 15;9(3):e13429. doi: 10.1016/j.heliyon.2023.e13429. eCollection 2023 Mar.
RFAP is a compound extraction complex of four Traditional Chinese Medicine (TCM), including the dry bark of Pall. (Radix Paeoniae Alba), J. Ellis (Fructus Gardeniae), Durazz. (Albizia julibrissin Durazz), and Andrews (Peony bark). Not only RFAP but also the individual ingredients have been commonly used for the treatment of depression in the clinic. However, the underlying mechanism of pharmacology is difficult to interpret since its holistic and multidrug nature.
This study aimed to elucidate the potential antidepressant mechanism of RFAP in the treatment of chronic unpredictable mild stress (CUMS) rats' model via the quantitative proteomics approach.
We established the CUMS rats' model and evaluated the efficacy of RFAP using multiple behavior assays, including the sugar preference test, open field test, and forced swimming test. Then label-free quantitative proteomics analyses were performed to evaluate the integrated changes of proteome profiling in control, CUMS, RFAP low dose, and RFAP high dose groups. Finally, we validated the critical changed proteins in the pathways of long-term depression and potentiation via RT-PCR and Western blotting assays.
We successfully established the CUMS rats' model. The behavior assays indicated that the rats demonstrated a tendency to behavioral despair after four weeks. Label-free quantitative proteomics showed that 107 proteins were significantly upregulated and 163 proteins were downregulated in the CUMS group compared to the control group. These differentially expressed proteins were involved in long-term potentiation, long-term depression, nervous system development, neuronal synaptic structural constituent of ribosome, ATP metabolic process, learning or memory, and cellular lipid metabolic process. RFAP treatment partially restored the differentially expressed protein profile. The protective effect of RFAP on behavioral assessment were consistent with the results of proteomics.
The results indicated that RFAP exerted a synergistic effect on CUMS by regulating long-term inhibition and potentiation-related proteins.
解郁方（RFAP）是一种由四种中药组成的复方提取物，包括芍药（白芍）的干燥根皮、栀子（栀子）、合欢（合欢皮）和牡丹（牡丹皮）。不仅解郁方，其各个成分在临床上也常用于治疗抑郁症。然而，由于其整体和多药性质，其潜在的药理机制难以解释。
本研究旨在通过定量蛋白质组学方法阐明解郁方治疗慢性不可预测轻度应激（CUMS）大鼠模型的潜在抗抑郁机制。
我们建立了CUMS大鼠模型，并使用多种行为学试验评估解郁方的疗效，包括糖水偏好试验、旷场试验和强迫游泳试验。然后进行无标记定量蛋白质组学分析，以评估对照组、CUMS组、解郁方低剂量组和解郁方高剂量组蛋白质组图谱的综合变化。最后，我们通过RT-PCR和蛋白质免疫印迹试验验证了长期抑郁和增强通路中关键变化的蛋白质。
我们成功建立了CUMS大鼠模型。行为学试验表明，四周后大鼠表现出行为绝望的倾向。无标记定量蛋白质组学显示，与对照组相比，CUMS组中有107种蛋白质显著上调，163种蛋白质下调。这些差异表达的蛋白质参与了长期增强、长期抑郁、神经系统发育、核糖体的神经元突触结构组成、ATP代谢过程、学习或记忆以及细胞脂质代谢过程。解郁方治疗部分恢复了差异表达的蛋白质谱。解郁方对行为评估的保护作用与蛋白质组学结果一致。
结果表明，解郁方通过调节与长期抑制和增强相关的蛋白质对CUMS发挥协同作用。
