School of Pharmacy, School of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, Shangdong 250355, P.R. China.
Institute of Traditional Chinese Medicine Basic Theory, School of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, Shangdong 250355, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3575-3582. doi: 10.3892/mmr.2017.8339. Epub 2017 Dec 22.
Depressive disorder (DD) is one of the typical affective disorders with a high morbidity, high suicide rate and high recurrence rate. Dysfunction of the 5‑hydroxytryptamine 1A receptor (5‑HT1AR) in the brain may serve an important role in the pathogenesis of DD. Currently, selective serotonin reuptake inhibitors are the first line antidepressants with 60‑70% efficacy and severe adverse effects. Previous studies have demonstrated that Chinese herbal medicines, including the Shuyu capsule (SYC), are effective antidepressants with few side effects. However, the mechanism remains unclear. In the present study, the effects of the SYC on the 5‑HT1AR level and the activation of adenylyl cyclase‑cyclic adenosine monophosphate (cAMP)‑protein kinase A (PKA)‑cAMP response element‑binding (CREB) signaling pathway that 5‑HT1AR mediates in the cells of hippocampal neurons were investigated in vitro. The SYC demonstrated an antidepressant effect similar to that of fluoxetine in a rat depression model. Treatment of hippocampal neurons with the serum of depressive rats resulted in a decrease in the 5‑HT1AR protein level and the activation of the cAMP‑PKA‑CREB signaling pathway in hippocampal neurons. Exposure to the serum of rats that received chronic mild stress plus SYC treatment led to no alterations in the 5‑HT1AR level or the activation of the cAMP‑PKA‑CREB signaling pathway compared with those of cells exposed to normal rat serum. This effect is similar to the effects of 5‑HT1AR antagonist WAY‑100635. In addition, the 5‑HT1A agonist 8‑hydroxy‑(dipropylamino) tetralin did not antagonize the effects of the SYC. Furthermore, the SYC exhibited an increased effect compared with fluoxetine on 5‑HT1AR levels and CREB activation. The present study suggested that the SYC functions by increasing 5‑HT1AR protein levels and the activation of the 5‑HT1AR‑mediated cAMP‑PKA‑CREB signaling pathway in hippocampal neurons.
抑郁障碍（DD）是一种典型的情感障碍，具有高发病率、高自杀率和高复发率。大脑中 5-羟色胺 1A 受体（5-HT1AR）的功能障碍可能在 DD 的发病机制中起重要作用。目前，选择性 5-羟色胺再摄取抑制剂是一线抗抑郁药，有效率为 60-70%，但不良反应严重。先前的研究表明，包括舒郁胶囊（SYC）在内的中草药是有效的抗抑郁药，副作用较少。然而，其机制尚不清楚。在本研究中，SYC 对海马神经元细胞中 5-HT1AR 介导的环磷酸腺苷（cAMP）-蛋白激酶 A（PKA）-cAMP 反应元件结合（CREB）信号通路的 5-HT1AR 水平和活性的影响进行了研究。SYC 在大鼠抑郁模型中表现出与氟西汀相似的抗抑郁作用。用抑郁大鼠血清处理海马神经元会导致海马神经元中 5-HT1AR 蛋白水平降低和 cAMP-PKA-CREB 信号通路激活。与正常大鼠血清处理的细胞相比，暴露于接受慢性轻度应激加 SYC 治疗的大鼠血清中，5-HT1AR 水平或 cAMP-PKA-CREB 信号通路的激活没有改变，这种作用类似于 5-HT1AR 拮抗剂 WAY-100635 的作用。此外，5-HT1A 激动剂 8-羟基-（二丙基氨基）四氢呋喃不能拮抗 SYC 的作用。此外，SYC 对 5-HT1AR 水平和 CREB 激活的作用比氟西汀更强。本研究表明，SYC 通过增加海马神经元中 5-HT1AR 蛋白水平和 5-HT1AR 介导的 cAMP-PKA-CREB 信号通路的激活来发挥作用。
