Flavonoids are bioactive compounds that are known to be neuroprotective against glutamate-mediated excitotoxicity, one of the major causes of neurodegeneration. The mechanisms underlying these effects are unresolved, but recent evidence indicates flavonoids may modulate estrogen signaling, which can delay the onset and ameliorate the severity of neurodegenerative disorders. Furthermore, the roles played by glial cells in the neuroprotective effects of flavonoids are poorly understood. The aim of this study was to investigate the effects of the flavonoid agathisflavone (FAB) in primary neuron-glial co-cultures from postnatal rat cerebral cortex. Compared to controls, treatment with FAB significantly increased the number of neuronal progenitors and mature neurons, without increasing astrocytes or microglia. These pro-neuronal effects of FAB were suppressed by antagonists of estrogen receptors (ERα and ERβ). In addition, treatment with FAB significantly reduced cell death induced by glutamate and this was associated with reduced expression levels of pro-inflammatory (M1) microglial cytokines, including TNFα, IL1β and IL6, which are associated with neurotoxicity, and increased expression of IL10 and Arginase 1, which are associated with anti-inflammatory (M2) neuroprotective microglia. We also observed that FAB increased neuroprotective trophic factors, such as BDNF, NGF, NT4 and GDNF. The neuroprotective effects of FAB were also associated with increased expression of glutamate regulatory proteins in astrocytes, namely glutamine synthetase (GS) and Excitatory Amino Acid Transporter 1 (EAAT1). These findings indicate that FAB acting via estrogen signaling stimulates production of neurons in vitro and enhances the neuroprotective properties of microglia and astrocytes to significantly ameliorate glutamate-mediated neurotoxicity.

中文翻译：

---

Agathisflavone是一种来自Poincianella pyramidalis（Tul。）的类黄酮，可增强神经元种群并防止谷氨酸兴奋性毒性。

类黄酮是已知对谷氨酸介导的兴奋性毒性具有神经保护作用的生物活性化合物，谷氨酸介导的兴奋性毒性是神经变性的主要原因之一。这些作用的潜在机制尚不清楚，但最近的证据表明类黄酮可能会调节雌激素信号传导，从而延迟发病并改善神经退行性疾病的严重程度。此外，对神经胶质细胞在类黄酮的神经保护作用中所起的作用了解甚少。这项研究的目的是调查黄酮类药物agathisflavone（FAB）在产后大鼠大脑皮层的原代神经元-胶质细胞共培养中的作用。与对照组相比，FAB治疗可显着增加神经元祖细胞和成熟神经元的数量，而不会增加星形胶质细胞或小胶质细胞。FAB的这些前神经元作用被雌激素受体拮抗剂（ERα和ERβ）抑制。此外，FAB的治疗可显着减少谷氨酸诱导的细胞死亡，这与促炎性（M1）小胶质细胞因子（包括TNFα，IL1β和IL6）的表达水平降低有关，这些因子与神经毒性有关，并增加IL10和与抗炎（M2）神经保护性小胶质细胞相关的精氨酸酶1。我们还观察到FAB增加了神经保护营养因子，例如BDNF，NGF，NT4和GDNF。FAB的神经保护作用还与星形胶质细胞（即谷氨酰胺合成酶（GS）和兴奋性氨基酸转运蛋白1（EAAT1））中谷氨酸调节蛋白的表达增加有关。