Pinocembrin mitigates depressive-like behaviors induced by chronic unpredictable mild stress through ameliorating neuroinflammation and apoptosis

Pinocembrin mitigates depressive-like behaviors induced by chronic unpredictable mild stress through ameliorating neuroinflammation and apoptosis
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Pinocembrin 通过改善神经炎症和细胞凋亡来减轻由慢性不可预测的轻度应激引起的抑郁样行为

DOI:
10.1186/s10020-020-00179-x
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发表时间:
2020-05
期刊:
影响因子:
5.7
通讯作者:
Gu Xunhu
Gu Xunhu
中科院分区:
医学2区
文献类型:
--
作者:
Wang Wei;Zheng Lili;Xu Lijun;Tu Jianglong;Gu Xunhu

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背景大多数慢性疲劳患者有抑郁症合并症的风险。 Pinocembrin (PB) 是从蜂蜜和蜂胶中分离出来的一种黄酮类分子,具有抗菌、抗炎、抗氧化和抗癌功能。本研究的目的是确定PB治疗抑郁症的可能功能。方法建立慢性不可预测轻度应激(CUMS)小鼠模型来模拟体内抑郁样行为。通过蔗糖偏好试验(SPT)、旷场试验(OFT)、强迫游泳试验(FST)和悬尾试验(TST)测量CUMS小鼠的抑郁样行为。采用商业试剂盒检测活性氧(ROS)、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性。检测炎症因子包括白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、IL-10和转化生长因子(TGF)-β。结果发现PB缓解了蔗糖偏好和体重的下降。 CUMS 小鼠在 FST 中显着增加了不动时间,但缩短了放弃潜伏期,在 TST 中增加了不动时间,在 OFT 中降低了交叉得分和饲养得分,而这些变化通过 PB 治疗而逆转。更重要的是,PB 降低了 ROS 和 MDA 的浓度,但增加了 SOD 活性,表明它可以保护 CUMS 小鼠免受氧化应激。有趣的是,PB 抑制 CUMS 小鼠海马细胞凋亡并调节炎症因子表达。此外,PB 激活 Nrf2/HO-1 信号通路,但抑制 NF-kB 磷酸化。结论 总之,PB 通过改善神经炎症和细胞凋亡减轻 CUMS 诱导的抑郁样行为。试验注册不适用。
BackgroundThe majority of patients with chronic fatigue have a risk of comorbidity with depression. Pinocembrin (PB) is a kind of flavonoid molecule isolated from honey and propolis and has antimicrobial, anti-inflammatory, antioxidant, and anticancer function. The purpose of the current study was to determine the possible function of PB on treatment of depression.MethodsA chronic unpredictable mild stress (CUMS) mouse model was established to mimic the depressive-like behaviors in vivo. The depressive-like behaviors of CUMS mice were measured by sucrose preference test (SPT), open field test (OFT), forced swim test (FST) and tail suspension test (TST). The concentration of reactive oxygen species (ROS), malondialdehyde (MDA) and the activity or superoxide dismutase (SOD) were detected by commercial kit. The inflammatory factor including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and transforming growth factor (TGF)-β were examined.ResultsWe found that PB alleviated the decreasing of sucrose preference and body weight. CUMS mice significantly increased the immobility time but decreased latency to abandon in FST, increased the immobility time in TST, and reduced crossing score and rearing score in OFT, whereas these changes were reversed by PB treatment. More importantly, PB decreased the concentration of ROS and MDA, but increased the SOD activity, suggesting that it could protected against oxidative stress in CUMS mice. Interestingly, PB inhibited cell apoptosis and regulated inflammatory factors expression in hippocampus of CUMS mice. Moreover, PB activated Nrf2/HO-1 signal pathway but inhibited the phosphorylation of NF-kB.ConclusionsIn conclusion, PB mitigated CUMS-induced depressive-like behaviors through ameliorating neuroinflammation and apoptosis.Trial registrationNot Applicable.
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