Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade
Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade
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DOI：
10.1007/s11011-019-0389-5
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发表时间：
2019-04-01
影响因子：
3.6
通讯作者：
Deng, Zhifang
中科院分区：
文献类型：
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作者：
Gao, Wenqi;Wang, Wei;Deng, Zhifang
山奈酚（KFL）是各种水果和蔬菜的主要成分，具有减轻氧化应激和炎症的作用。本研究旨在探讨KFL对慢性社会失败应激（CSDS）小鼠抑郁样行为的改善作用，并探讨其在氧化应激、神经炎症和AKT/-catenin信号通路中的潜在机制。采用蔗糖偏好测试（SPT）、社会互动测试（SIT）和悬尾测试（TST）三种行为测试来评估KFL对CSDS小鼠的抗抑郁作用。采用商品化试剂盒分别测定大鼠前额皮质抗氧化酶、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）、谷胱甘肽s-转移酶（GST）活性水平以及丙二醛（MDA）和蛋白羰化浓度。Elisa法检测血清白细胞介素-1 （IL-1）和肿瘤坏死因子（TNF-）水平。采用Q-PCR检测CD-11b mRNA表达水平。western blot检测CSDS小鼠前额皮质AKT/-catenin信号通路的活性水平。此外，我们利用PI3-K抑制剂LY294002来研究AKT/-catenin信号通路在KFL抗抑郁作用中的作用。社交失败压力降低了小鼠的体重、蔗糖消耗、社交次数和悬尾活动次数。CSDS小鼠也表现出氧化应激标志物、炎症介质水平显著升高，前额皮质AKT/-catenin级联活性降低，KFL治疗可逆转这一现象。有趣的是，LY294002似乎部分抑制了CSDS小鼠中kfl介导的整体保护作用。这些结果证实，KFL具有抗抑郁作用，这可能至少部分是通过上调CSDS小鼠前额叶皮层AKT/-catenin级联活性来增强抗氧化能力和抗炎症作用。因此，KFL可能是一种有前景的、有效的、安全的治疗抑郁症的食品药物。
Kaempferol (KFL), the major constituent of various fruits and vegetables, could attenuate oxidaitve stress and inflammation. The aims of the present study were to explore the ameliorative abilities of KFL on the depressive-like behaviors in a chronic social defeat stress (CSDS) mouse model, and to determine the potential mechanisms on oxidative stress, neuroinflammation, and AKT/-catenin signaling pathway. Three behavioral tests, sucrose preference test (SPT), social interaction test (SIT), and tail suspension test (TST), were used to evaluate the antidepressive effects of KFL in CSDS mice. Activity levels of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione s-transferase (GST), and concentrations of malonaldehyde (MDA) and protein carbonylation in the prefrontal cortex were assessed by commercial kits, respectively. Elisa was used to detect the levels of interleukin-1 (IL-1) and tumor necrosis factor (TNF-). Q-PCR was used to determine the mRNA level of CD-11b. Furthermore, activity level of AKT/-catenin signaling in the prefrontal cortex of CSDS mice was investigated by western blot. In addition, LY294002, a PI3-K inhibitor, was used to investigate the role of AKT/-catenin signaling in the antidepressant effects of KFL. Social defeat stress reduced the bodyweights, sucrose consumptions, social interaction times, and the tail suspension mobility times in mice. CSDS mice were also exhibited remarkablely increased levels in oxidative stress markers, inflammatory mediators, and decreased activity of AKT/-catenin cascade in the prefrontal cortex, which were reversed by treatment with KFL. Interestingly, LY294002 appeared to partly inhibit the overall KFL-mediated protective effects in the CSDS mice. These results confirmed that KFL exerted antidepressive effects, which might be mediated, at least in part, by enhanced antioxidant abilities and anti-inflammation effects via up-regulation AKT/-catenin cascade activity in the prefrontal cortex of CSDS mice. Thus, KFL might be a promising, effective, and safe food medicine for depression treatment.