Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin’s anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where alterations in numerous processes are observed. However, the extent of baicalin’s therapeutic effects remains undetermined in a human cell model, more specifically, neuronal cells to mimic the brain environment in vitro. As a proof of concept, we treated C8-B4 cells (murine cell model) with three different doses of baicalin (0.1, 1 and 5 μM) and vehicle control (DMSO) for 24 h after liposaccharide-induced inflammation and measured the levels of TNF-α in the medium by ELISA. NT2-N cells (human neuronal-like cell model) underwent identical baicalin treatment, followed by RNA extraction, genome-wide mRNA expression profiles and gene set enrichment analysis (GSEA). We also performed neurite outgrowth assays and mitochondrial flux bioanalysis (Seahorse) in NT2-N cells. We found that in C8-B4 cells, baicalin at ≥ 1 μM exhibited anti-inflammatory effects, lowering TNF-α levels in the cell culture media. In NT2-N cells, baicalin positively affected neurite outgrowth and transcriptionally up-regulated genes in the tricarboxylic acid cycle and the glycolysis pathway. Similarly, Seahorse analysis showed increased oxygen consumption rate in baicalin-treated NT2-N cells, an indicator of enhanced mitochondrial function. Together, our findings have confirmed the neuroprotective and mitochondria enhancing effects of baicalin in human-neuronal like cells. Given the increased prominence of mitochondrial mechanisms in diverse neuropsychiatric disorders and the paucity of mitochondrial therapeutics, this suggests the potential therapeutic application of baicalin in human neuropsychiatric disorders where these processes are altered.

黄芩苷是一种从黄芩属开花植物中提取的黄酮苷。先前的研究报道了黄芩苷在啮齿动物模型中的抗炎和神经保护特性，表明黄芩苷在神经精神疾病中的潜力，在神经精神疾病中观察到了许多过程的改变。然而，黄芩苷在人体细胞模型中的治疗效果仍不确定，更具体地说，在模拟体外大脑环境的神经元细胞中。作为概念证明，我们在脂糖诱导炎症后用三种不同剂量的黄芩苷（0.1、1 和 5 μM）和载体对照 (DMSO) 处理 C8-B4 细胞（小鼠细胞模型）24 小时，并测量通过 ELISA 检测培养基中的 TNF-α。NT2-N 细胞（人类神经元样细胞模型）接受相同的黄芩苷处理，然后进行 RNA 提取、全基因组 mRNA 表达谱和基因集富集分析 (GSEA)。我们还在 NT2-N 细胞中进行了神经突生长测定和线粒体通量生物分析 (Seahorse)。我们发现在 C8-B4 细胞中，≥ 1 μM 的黄芩苷表现出抗炎作用，降低细胞培养基中的 TNF-α 水平。在 NT2-N 细胞中，黄芩苷对神经突生长和三羧酸循环和糖酵解途径中的转录上调基因产生积极影响。同样，Seahorse 分析显示黄芩苷处理的 NT2-N 细胞耗氧率增加，这是线粒体功能增强的指标。总之，我们的研究结果证实了黄芩苷在人类神经元样细胞中的神经保护和线粒体增强作用。鉴于线粒体机制在多种神经精神疾病中的重要性日益突出，并且线粒体治疗方法的缺乏，这表明黄芩苷在这些过程发生改变的人类神经精神疾病中具有潜在的治疗应用。