Myricetin alleviates the mechanism of IL-1β production caused by the endocrine-disrupting chemical Di(2-ethylhexyl) phthalate in RAW 264.7 cells.

Abstract

Myricetin, a flavonoid present in numerous fruits, vegetables, and medicinal plants, is recognized for its potent antioxidant, anti-inflammatory, and anti-cancer activities. Nevertheless, its involvement in mitigating inflammation caused by the endocrine-disrupting chemical Di(2-ethylhexyl) phthalate (DEHP), commonly used in polyvinyl chloride (PVC) manufacturing to improve flexibility, has not been investigated. Here, we found that DEHP markedly increased IL-1β production through inflammatory pathways in RAW 264.7 murine macrophages. Treatment with myricetin at a concentration of 10 μM significantly reduced the elevated IL-1β levels. Myricetin achieves this by inhibiting the activation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), which are driven by reactive oxygen species (ROS), thereby suppressing IL-1β transcription via nuclear factor-kappa B (NF-κB). Additionally, myricetin prevents ROS-induced activation of the NLRP3 inflammasome and subsequent caspase-1 activation, further decreasing IL-1β production. These dual actions highlight myricetin's therapeutic potential in countering the oxidative stress-mediated inflammatory pathways triggered by environmental toxins like DEHP.