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
MDMA activates microglia in the brain, leading to neurotoxicity and increased inflammatory gene expression. Thymoquinone (TQ) was found to reduce these inflammatory responses in BV2 microglial cells activated by MDMA. Specifically, TQ pre-treatment decreased morphological changes and inhibited several pro-inflammatory genes associated with MDMA-induced activation. Overall, TQ demonstrates neuroprotective effects against the harmful activation of microglia caused by MDMA.
Study at a glance
| Population | BV2 microglial cells |
|---|---|
| Key finding | Thymoquinone (TQ) reduces inflammatory responses and stabilizes microglial activation induced by MDMA. |
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.