Background <p>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 <i>Araucaria angustifolia</i> (AAE) was tested to explore a possible therapeutic intervention.</p> Methods and results <p>BV-2 cell line was exposed to LPS (10&#xa0;µg/mL) <i>plus</i> KYN (1000 µM), and afterward, the ability of AAE (25&#xa0;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 (<i>p</i> &lt; 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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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The protective effects of Araucaria angustifolia (Bertol.) on neurodegeneration induced by LPS and kynurenine exposure in BV-2 microglial cells

  • Ana Paula Vargas Visentin,
  • Júlia Maiara Santos,
  • Amanda Pereira,
  • Fernando Joel Scariot,
  • Andiara Prates Ramos,
  • Luciana Bavaresco Touguinha,
  • Alencar Kolinski Machado,
  • Mirian Salvador,
  • Catia Santos Branco

摘要

Background

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.

Methods and results

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.

Conclusions

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.

Graphical Abstract