Introduction: Depression is one of the most common neuropsychiatric illnesses which leads to a huge social and economic burden on modern society. So, it is necessary to develop an effective and safe pharmacological intervention for depression. Accumulating evidence has shown that adenosine monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway plays a pivotal role in the development of depression. Our present study aimed to investigate the antidepressant effect and possible mechanisms of salvianolic acid B (SalB) in a chronic mild stress (CMS)-induced depression model in rats.
Materials and Methods: The rats were randomly divided into three groups: control group with no stressor, CMS group and CMS+SalB (30 mg/kg/d) group. After administration for 28 consecutive days, the behavior tests were performed. The rats were sacrificed after behavior tests, and the brain tissues were collected for biochemical analysis.
Results: It was observed that the administration of SalB for 28 consecutive days successfully corrected the depressive-like behaviors in CMS-treated rats. SalB could effectively reduce the gene expression of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), as well as nuclear factor-kappa B (NF-κB) p65 protein. In addition, inhibitor of NF-κB (IκB) protein expression was significantly increased after the administration of SalB. Moreover, SalB could effectively decrease protein expression of oxidative stress markers such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) and increase the activity of catalase (CAT). SalB treatment also reversed CMS-induced inhibition of Nrf2 signaling pathway, along with increasing the mRNA expression of NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1). Regarding the endoplasmic reticulum (ER) stress markers, the protein expressions of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 kD (GRP78) were also significantly reduced after SalB administration. Furthermore, the supplementation of SalB could effectively activate the AMPK/SIRT1 signaling pathway, which indicated significant increase in pAMPK/AMPK ratio and SIRT1 protein expression.
Conclusion: Our study demonstrated that SalB relieved CMS-induced depressive-like state through the mitigation of inflammatory status, oxidative stress, and the activation of AMPK/SIRT1 signaling pathway.

Keywords: SalB, depression, CMS, AMPK/SIRT1


中文翻译：

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Salvianolic Acid B 改善大鼠慢性轻度应激诱导的抑郁行为：AMPK/SIRT1 信号通路的参与。

简介：抑郁症是最常见的神经精神疾病之一，给现代社会带来巨大的社会和经济负担。因此，有必要开发一种有效且安全的抑郁症药物干预措施。越来越多的证据表明，一磷酸腺苷活化蛋白激酶/sirtuin 1 (AMPK/SIRT1) 信号通路在抑郁症的发展中起关键作用。我们目前的研究旨在探讨丹酚酸 B (SalB) 在大鼠慢性轻度应激 (CMS) 诱导的抑郁模型中的抗抑郁作用和可能的机制。
材料和方法：将大鼠随机分为三组：无应激对照组、CMS组和CMS+SalB（30 mg/kg/d）组。连续给药28天后，进行行为测试。行为测试后处死大鼠，采集脑组织进行生化分析。
结果：观察到连续 28 天施用 SalB 成功地纠正了 CMS 治疗大鼠的抑郁样行为。SalB可有效降低促炎细胞因子如白细胞介素6（IL-6）、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）以及核因子-κB的基因表达(NF-κB) p65 蛋白。此外，在施用 SalB 后，NF-κB 抑制剂 (IκB) 蛋白表达显着增加。此外，SalB 可有效降低 4-羟基壬烯醛 (4-HNE) 和丙二醛 (MDA) 等氧化应激标志物的蛋白表达，提高过氧化氢酶 (CAT) 的活性。SalB 治疗还逆转了 CMS 诱导的 Nrf2 信号通路抑制，同时增加了 NAD(P)H 的 mRNA 表达：醌氧化还原酶 (NQO-1) 和血红素加氧酶 1 (HO-1)。关于内质网 (ER) 应激标志物，SalB 给药后 C/EBP 同源蛋白 (CHOP) 和葡萄糖调节蛋白 78 kD (GRP78) 的蛋白质表达也显着降低。此外，添加 SalB 可有效激活 AMPK/SIRT1 信号通路，这表明 pAMPK/AMPK 比值和 SIRT1 蛋白表达显着增加。
结论：我们的研究表明，SalB 通过减轻炎症状态、氧化应激和激活 AMPK/SIRT1 信号通路来缓解 CMS 诱导的抑郁样状态。

关键词： SalB，抑郁症，CMS，AMPK/SIRT1