Ferulic acid attenuates oxidative DNA damage and inflammatory responses in microglia induced by benzo(a)pyrene
Yongfen Bao1, Qingjie Chen2, Yushuang Xie3
1Research Center of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, China.
Abstract:
Over-activation of microglia disrupts the physiological homeostasis of the brain, and induces inflammatory response and other processes which are implicated in neurodegenerative diseases. Therefore, theoretically, suppression of neuroinflammation would slow the progression of neurodegenerative disease. In this study, we investigated the possible protective effects of Ferulic acid (FA) against benzo(a)pyrene (BaP)-induced microglial activation using BV2 cells as the model system. Exposure of BV2 cells to BaP (10 μM) significantly increased DNA damage and the production of pro-inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), malondialdehyde (MDA), and cytokines (interleukins-1β and -6). On the other hand, when BaP-treated BV2 cells were further incubated with FA (10, 20, 40, or 80 mg/mL) for another 24 h, a significant reduction in BaP-induced DNA damage and the release of multiple pro-inflammatory and cytotoxic factors (including interleukin-1β, interleukin-6, NO, and ROS) was observed in a dose-dependent manner. Further study revealed that the microglial NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) signaling pathway was involved in the protective effect of FA. Taken together, these results suggested that FA suppressed BaP-induced toxicity in microglia, and thus may exert neuroprotective effects by inhibiting microglia-mediated pro-inflammatory response.
Insights
Ferulic acid (FA) protects against benzo(a)pyrene (BaP) induced microglial activation. FA reduces DNA damage and inflammatory factors, suggesting neuroprotective potential by inhibiting microglia-mediated inflammation.
Area of Science:
- Neuroscience
- Neuroinflammation Research
- Cellular Biology
Background:
- Microglial over-activation disrupts brain homeostasis and contributes to neurodegenerative diseases.
- Neuroinflammation is a key process implicated in the progression of neurodegenerative conditions.
- Targeting microglial activation offers a potential therapeutic strategy for neuroprotection.
Purpose of the Study:
- To investigate the protective effects of Ferulic acid (FA) against benzo(a)pyrene (BaP)-induced microglial activation.
- To determine if FA can mitigate the inflammatory response and cellular damage caused by BaP in microglia.
- To explore the underlying molecular mechanisms, including the NLRP3 inflammasome pathway, involved in FA's protective effects.
Main Methods:
- Utilized BV2 cells as a model system for microglial activation.
- Exposed BV2 cells to benzo(a)pyrene (BaP) and subsequently treated with varying concentrations of Ferulic acid (FA).
- Assessed DNA damage, nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), and cytokine (IL-1β, IL-6) production. Investigated the role of the NLRP3 inflammasome pathway.
Main Results:
- BaP exposure significantly increased DNA damage and pro-inflammatory mediators (NO, iNOS, COX-2, ROS, MDA, IL-1β, IL-6) in BV2 cells.
- Ferulic acid (FA) treatment dose-dependently reduced BaP-induced DNA damage and the release of pro-inflammatory and cytotoxic factors (IL-1β, IL-6, NO, ROS).
- The protective effect of FA was associated with the modulation of the microglial NLRP3 inflammasome signaling pathway.
Conclusions:
- Ferulic acid (FA) demonstrates significant protective effects against benzo(a)pyrene (BaP)-induced toxicity in microglia.
- FA suppresses BaP-induced microglial activation, DNA damage, and the production of inflammatory mediators.
- These findings suggest that FA holds potential as a neuroprotective agent by inhibiting microglia-mediated pro-inflammatory responses.
