Phytoestrogens can control high‐fat diet‐induced hypothalamic inflammation that is associated with severe consequences, including obesity, type 2 diabetes, cardiovascular and neurodegenerative diseases. However, the phytoestrogen anti‐neuroinflammatory action is poorly understood. In this study, we explored the neuroprotection mediated by daidzein in hypothalamic neurons by using a membrane‐based model of obesity‐related neuroinflammation. To test the daidzein therapeutic potential a biohybrid membrane system, consisting of hfHypo GnRH‐neurons in culture on PLGA membranes, was set up. It served as reliable in vitro tool capable to recapitulate the in vivo structure and function of GnRH hypothalamic tissue. Our findings highlighted the neuroprotective role of daidzein, being able to counteract the palmitate induced neuroinflammation. Daidzein protected hfHypo GnRH cells by downregulating cell death, proinflammatory processes, oxidative stress, and apoptosis. It also restored the proper cell morphology and functionality through a mechanism which probably involves the activation of ERβ and GPR30 receptors along with the expression of GnRH peptide and KISS1R.

中文翻译：

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黄豆苷元在体外膜模型中对人下丘脑 GnRH 神经元的抗神经炎症作用

植物雌激素可以控制高脂肪饮食引起的下丘脑炎症，这种炎症会导致严重的后果，包括肥胖、2 型糖尿病、心血管和神经退行性疾病。然而，植物雌激素的抗神经炎症作用知之甚少。在这项研究中，我们使用基于膜的肥胖相关神经炎症模型探索了下丘脑神经元中黄豆苷元介导的神经保护作用。为了测试黄豆苷元的治疗潜力，建立了一个生物混合膜系统，该系统由在 PLGA 膜上培养的 hfHypo GnRH 神经元组成。它作为可靠的体外工具，能够概括 GnRH 下丘脑组织的体内结构和功能。我们的研究结果强调了黄豆苷元的神经保护作用，能够抵消棕榈酸酯诱导的神经炎症。大豆苷元通过下调细胞死亡、促炎过程、氧化应激和细胞凋亡来保护 hfHypo GnRH 细胞。它还通过可能涉及激活 ERβ 和 GPR30 受体以及 GnRH 肽和 KISS1R 表达的机制恢复了正确的细胞形态和功能。