The Potential Neuroinflammatory Attenuation Effects of Thymoquinone against 3, 4-Methylenedioxymethamphetamine-Induced Microglial Activation in BV2 Mouse Cell Line
Nor Suliana Mustafa, Nasir Mohamad, Nor Hidayah Abu Bakar, Holifa Saheera Asmara, Mohd Nazri Mohd Daud, Liyana Hazwani Mohd Adnan
bioRxiv Preprint Server June 16, 2025 preprint DOI: 10.1101/2025.06.16.660054 via bioRxiv
Summary
AI-generated from the abstractMDMA activates microglia in the brain, causing morphological changes and inflammatory responses that can lead to neurotoxicity. Thymoquinone (TQ), a compound with known anti-inflammatory properties, was tested on BV2 microglial cells to see if it could counteract MDMA's effects. Transcriptome analysis showed that MDMA significantly increased cytokines, chemokines, and inflammation-related genes. Pre-treatment with TQ reduced morphological changes in microglia and lowered the expression of several pro-inflammatory genes, including Cxcl2, Ptgs2, C3ar1, Nfkbia, Il1a, Cxcl10, and Serpinf2. The findings suggest that TQ has neuroprotective effects against MDMA-induced microglial activation by stabilizing microglial activity.
Study at a glance
| Characteristics | In vitro study |
|---|---|
| Population | BV2 microglial cells |
| Interventions | Thymoquinone MDMA |
| Key finding | Thymoquinone reduced inflammatory responses in MDMA-induced microglial activation by inhibiting several pro-inflammatory genes. |
Abstract
MDMA induced the activation of microglia in the brain which would lead to neurotoxicity. The activation of microglia is associated with morphological changes and the production of inflammatory phenotypes. While there is research suggesting that thymoquinone (TQ) may have anti-inflammatory effects and modulate microglial activation, studies specifically focusing on its impact on activated microglia induced by MDMA or Ecstasy appear to be limited or not yet available. In this study, the effects of MDMA and TQ in BV2 microglial cells were examined to see the differences in gene expression profile, and whether TQ could modulate the inflammatory genes in MDMA-induced BV2 microglial activation. Transcriptome analysis revealed that cytokines/chemokines and inflammation-related genes were significantly up-regulated in response to MDMA-induced microglial activation. TQ pre-treatment in the MDMA+TQ group appeared to have attenuated the morphological changes of microglia as compared to the MDMA group. RNA-Seq analysis revealed that TQ reduced inflammatory responses in MDMA-induced microglial activation by inhibiting the production of several pro-inflammatory genes such as Cxcl2, Ptgs2, C3ar1, Nfkbia, Il1a, Cxcl10, and Serpinf2 (P≤0.05). This study concluded that TQ possesses neuroprotective effects against MDMA-induced microglial activation by stabilizing the effects of microglia.