Visentin Ana Paula Vargas, Santos Júlia Maiara, Pereira Amanda, Scariot Fernando Joel, Ramos Andiara Prates, Touguinha Luciana Bavaresco, Machado Alencar Kolinski, Salvador Mirian, Branco Catia Santos
Oxidative Stress & Antioxidants Laboratory, Institute of Biotechnology, Caxias do Sul, University of Caxias do Sul, Caxias do Sul, Rio Grande do Sul, Brazil.
Neurotoxicity & Neuroprotection Research Laboratory, Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mol Biol Rep. 2025 May 30;52(1):517. doi: 10.1007/s11033-025-10637-6.
The interplay between chronic inflammation, redox imbalance, apoptosis, and mitochondrial dysfunction is a central key in brain disorders (BD). This study aimed to develop an in vitro model using BV-2 microglial cells treated sequentially with lipopolysaccharide (LPS) and kynurenine (KYN) to mimic chronic biochemical changes observed in BD. Moreover, a polyphenol-rich extract from Araucaria angustifolia (AAE) was tested to explore a possible therapeutic intervention.
BV-2 cell line was exposed to LPS (10 µg/mL) plus KYN (1000 µM), and afterward, the ability of AAE (25 µg/mL) to reduce the changes induced by LPS + KYN was evaluated. As expected, the LPS + KYN combination reduced cell viability, increased reactive oxygen species production, compromised mitochondrial integrity, reduced ATP biosynthesis, and increased apoptosis rates (p < 0.05), perpetuating a self-sustaining inflammatory cycle. These changes (except inflammatory markers) were prevented by treatment with AAE, indicating the potential of this natural product as a possible adjuvant agent in treating patients with BD.
Although in vitro studies do not replace in vivo models, the system proposed in this study can help better understand the biochemical changes in the glial microenvironment and serve as a preliminary screening of future drugs or herbal medicines for mitigating or reversing neurotoxic outcomes.
慢性炎症、氧化还原失衡、细胞凋亡和线粒体功能障碍之间的相互作用是脑部疾病（BD）的核心关键因素。本研究旨在建立一种体外模型，使用经脂多糖（LPS）和犬尿氨酸（KYN）依次处理的BV-2小胶质细胞，以模拟BD中观察到的慢性生化变化。此外，还测试了南洋杉富含多酚的提取物（AAE），以探索可能的治疗干预措施。
将BV-2细胞系暴露于LPS（10 μg/mL）加KYN（1000 μM），随后评估AAE（25 μg/mL）减轻LPS+KYN诱导变化的能力。正如预期的那样，LPS+KYN组合降低了细胞活力，增加了活性氧的产生，损害了线粒体完整性，降低了ATP生物合成，并增加了凋亡率（p<0.05），从而维持了一个自我维持的炎症循环。AAE处理可预防这些变化（炎症标志物除外），表明这种天然产物作为治疗BD患者的可能辅助药物的潜力。
虽然体外研究不能替代体内模型，但本研究提出的系统有助于更好地理解胶质微环境中的生化变化，并作为未来减轻或逆转神经毒性结果的药物或草药的初步筛选。
