微胶质细胞诱导的神经炎症是认知功能障碍和神经退行性疾病的诱因之一。我们以前的研究发现，忘忧草提取物（Brainon®）对中枢神经系统有多种益处，但其作用机制尚未阐明。本研究旨在调查Brainon在BV-2细胞系SH-SY5Y模型中的抗炎和神经保护机制。使用脂多糖（LPS）诱导的BV-2细胞培养物（CM）处理SH-SY5Y细胞，以研究提取物对微胶质细胞细胞毒作用的神经保护作用。结果表明，Brainon预处理减少了亚硝酸盐释放、诱导性一氧化氮合酶表达水平和细胞因子，如白细胞介素6、白介素1β和肿瘤坏死因子α的表达，通过阻止TLR4 / MyD88和NLRP3的表达，抑制核因子κB / AP-1和p38 / JNK信号通路，在LPS诱导的BV-2细胞中。另外，当SH-SY5Y细胞用CM处理时，Brainon预处理通过上调抗氧化蛋白的表达，如SOD和Gpx-1，提高了神经元的存活率。增加的自噬和线粒体自噬相关蛋白，也为SH-SY5Y细胞通过Brainon预防细胞凋亡提供了重要线索。 Brainon还通过调节mTOR / AMPK信号通路，调节自/线粒体噬菌体清除错折蛋白或受损线粒体，保护SH-SY5Y细胞免受CM的影响。综上所述，这些结果表明，Brainon可以减少由BV-2细胞分泌的炎症介质，并通过调节SH-SY5Y细胞中mTOR / AMPK信号通路的抗氧化和自/线粒体噬菌体机制来防止细胞凋亡。因此，Brainon具有作为大脑健康功能性食品中的天然产品开发的潜力，以抑制认知衰退和神经元死亡。

Microglia-induced neuroinflammation is one of the causative factors in cognitive dysfunction and neurodegenerative disorders. Our previous studies have revealed several benefits of Scrophularia buergeriana extract (Brainon®) in the central nervous system, but the underlying mechanism of action has not been elucidated. This study is purposed to investigate the anti-inflammatory and neuroprotective mechanisms of Brainon in the BV-2 condition SH-SY5Y model. Lipopolysaccharide (LPS)-induced BV-2 conditioned media (CM) were used to treat SH-SY5Y cells to investigate neuroprotective effects of the extract against microglial cytotoxicity. Results demonstrated that pretreated Brainon decreased nitric oxide release, the inducible nitric oxide synthase expression level, and expression of cytokines like interleukin-6, interleukin-1β, and tumor necrosis factor-α by blocking expression of TLR4/MyD88 and NLRP3 and suppressing nuclear factor κB/AP-1 and p38/JNK signaling pathways in LPS-induced BV-2 cells. In addition, when SH-SY5Y cells were treated with CM, pretreatment with Brainon increased neuronal viability by upregulating expression of antioxidant proteins like as SODs and Gpx-1. Increased autophagy and mitophagy-associated proteins also provide important clues for SH-SY5Y to prevent apoptosis by Brainon. Brainon also modulated mTOR/AMPK signaling to clear misfolded proteins or damaged mitochondria via auto/mitophagy to protect SH-SY5Y cells from CM. Taken together, these results indicate that Brainon could reduce inflammatory mediators secreted from BV-2 cells and prevent apoptosis by increasing antioxidant and auto/mitophagy mechanisms by regulating mTOR/AMPK signaling in SH-SY5Y cells. Therefore, Brainon has the potential to be developed as a natural product in a brain health functional food to inhibit cognitive decline and neuronal death.