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Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-07-01 , DOI: 10.1021/acschemneuro.0c00120 Xiang Xu 1 , Xiao-Yu Zeng 1 , Yue-Xian Cui 2 , Ying-Biao Li 2 , Jia-Hui Cheng 1 , Xu-Dong Zhao 1 , Guang-Hua Xu 1 , Juan Ma 1 , Hu-Nan Piao 2 , Xuejun Jin 1 , Lian-Xun Piao 1
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-07-01 , DOI: 10.1021/acschemneuro.0c00120 Xiang Xu 1 , Xiao-Yu Zeng 1 , Yue-Xian Cui 2 , Ying-Biao Li 2 , Jia-Hui Cheng 1 , Xu-Dong Zhao 1 , Guang-Hua Xu 1 , Juan Ma 1 , Hu-Nan Piao 2 , Xuejun Jin 1 , Lian-Xun Piao 1
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Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.
中文翻译：
Arctiin 通过 HMGB1/TLR4 和 TNF-α/TNFR1 介导的 NF-κB 激活减轻神经炎症的抗抑郁作用。
炎症是抑郁症病理生理学中的一个潜在因素。一种传统的中草药牛蒡子苷及其苷元牛蒡子苷元是牛蒡子的主要生物活性成分，具有神经保护和抗炎活性。据报道，牛蒡子素具有抗抑郁样作用。然而，牛蒡子素（其前体）的抗抑郁样作用仍然未知。在这项研究中，我们通过体内和体外研究了牛蒡素的抗抑郁样作用及其潜在机制。小鼠实验。我们的研究结果表明，牛蒡子苷显着减少了蔗糖的消耗，并增加了悬尾和强迫游泳试验中的不动时间。Arctiin 减少了大脑前额叶皮层 (PFC) 的神经元损伤。Arctiin 还减弱了三种炎症介质的水平，即吲哚胺 2,3-双加氧酶、5-羟色胺和多巴胺，它们在暴露于慢性不可预知轻度应激 (CUMS) 的小鼠的 PFC 或血清中升高。Arctiin 通过降低高迁移率组框 1 (HMGB1)/toll 样受体 4 (TLR4) 和肿瘤坏死因子-α (TNF-α)/TNF 受体 1 (TNFR1) 介导的核因子来减少小胶质细胞的过度激活和神经炎症CUMS 暴露小鼠和 HMGB1 或 TNF-α 刺激的原代培养小胶质细胞的 PFC 中的 -kappa B (NF-κB) 激活。
更新日期：2020-08-05
中文翻译：
Arctiin 通过 HMGB1/TLR4 和 TNF-α/TNFR1 介导的 NF-κB 激活减轻神经炎症的抗抑郁作用。
炎症是抑郁症病理生理学中的一个潜在因素。一种传统的中草药牛蒡子苷及其苷元牛蒡子苷元是牛蒡子的主要生物活性成分，具有神经保护和抗炎活性。据报道，牛蒡子素具有抗抑郁样作用。然而，牛蒡子素（其前体）的抗抑郁样作用仍然未知。在这项研究中，我们通过体内和体外研究了牛蒡素的抗抑郁样作用及其潜在机制。小鼠实验。我们的研究结果表明，牛蒡子苷显着减少了蔗糖的消耗，并增加了悬尾和强迫游泳试验中的不动时间。Arctiin 减少了大脑前额叶皮层 (PFC) 的神经元损伤。Arctiin 还减弱了三种炎症介质的水平，即吲哚胺 2,3-双加氧酶、5-羟色胺和多巴胺，它们在暴露于慢性不可预知轻度应激 (CUMS) 的小鼠的 PFC 或血清中升高。Arctiin 通过降低高迁移率组框 1 (HMGB1)/toll 样受体 4 (TLR4) 和肿瘤坏死因子-α (TNF-α)/TNF 受体 1 (TNFR1) 介导的核因子来减少小胶质细胞的过度激活和神经炎症CUMS 暴露小鼠和 HMGB1 或 TNF-α 刺激的原代培养小胶质细胞的 PFC 中的 -kappa B (NF-κB) 激活。
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