Baicalein antagonises Rhopilema esculentum toxin-induced oxidative stress and apoptosis by modulating ROS-MAPK-NF-κB and inhibiting PLA2 activity

Abstract

The toxicity of jellyfish Rhopilema esculentum (R. esculentum), an edible jellyfish that releases venom, has been controversial. The aim of this comprehensive study was to investigate the toxic effects of jellyfish tentacle extract (TE), which was evaluated in vivo and in vitro using ICR mice and RAW264.7 cells respectively. A library of natural compounds was screened for their ability to antagonize phospholipase A₂ (PLA₂) activity to identify potential protective agents and mechanisms. Of the 20 natural compounds evaluated, baicalein was found to have the strongest PLA₂ antagonistic and cytoprotective effects. In vivo, experiments showed that TE at a dose of 7.02 mg/kg only resulted in a 50% survival rate in mice. However, pretreatment with 30 mg/kg baicalein significantly increased the survival rate to 75%, while also attenuating TE-induced cardiac and hepatic injuries, and ameliorating TE-induced elevations in LDH, CK-MB, and AST levels. In vitro studies found that baicalein reduced cellular ROS and MDA levels, increased the expression of CAT, SOD, and GSH/GSSG to enhance cellular antioxidant defenses against TE-induced oxidative stress, and also inhibited TE-induced upregulation of TNF-α, IL-6, IL-1β, and CXCL10. Importantly, baicalein was found to modulate dysregulated MAPK and NF-κB signaling pathways disrupted by TE. Taken together, these findings suggest that baicalein can antagonize R. esculentum toxin-induced oxidative stress and apoptosis by modulating ROS/MAPK/NF-κB, which provides a viable therapeutic strategy to control the deleterious effects of jellyfish stings and associated inflammation.