N-(p-Coumaroyl) Serotonin Ameliorates LPS-Induced Inflammation in BV2 Microglia via MAPK/NF-κB Inactivation and HO-1/NQO1 Upregulation

TL;DR

N-(p-Coumaroyl) serotonin reduces inflammation in microglial cells by blocking harmful signaling pathways and boosting protective antioxidant systems.

Contribution

This study identifies a novel anti-inflammatory mechanism of N-(p-coumaroyl) serotonin in microglia via MAPK/NF-κB suppression and HO-1/NQO1 activation.

Findings

CS pretreatment reduced inflammatory cytokines IL-6, TNF-α, and MCP-1 in LPS-challenged microglia.

CS inhibited iNOS and COX-2 protein levels through MAPK/NF-κB pathway disruption.

CS activated HO-1/NQO1 and interfered with TLR4/MyD88 signaling to exert antioxidant effects.

Abstract

Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to elucidate the specific molecular mechanisms governing these effects. ELISA, nitric oxide (NO) assays, Western blotting and immunocytochemistry were performed to study inflammatory responses and related signal transduction mechanisms. CS pretreatment effectively attenuated the inflammatory output in endotoxin-primed microglial models. This was evidenced by a significant reduction in key cytokines (such as IL-6, TNF-α, and MCP-1) and a concomitant decrease in the protein levels of iNOS and COX-2. These effects were mediated through the disruption of MAPK/NF-κB signaling cascades and the sequestration of NF-κB within the cytoplasm. Beyond its anti-inflammatory role, CS promoted the HO-1/NQO1 signaling pathway and interfered with the LPS-mediated TLR4/MyD88 cascade. Our collective evidence indicates that the modulation of microglia-mediated inflammation by CS is underpinned by the suppression of MAPK/NF-κB and the induction of antioxidant systems, suggesting that CS may have the potential to improve NDs.

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