Oxymatrine antagonises oxidative stress and apoptosis in Nemopilema nomurai toxin-induced cardiotoxicity by inhibiting mitogen-activated protein kinase

Jellyfish stings can trigger abrupt heart failure via toxins, leading acute mortality rise. Proposed mechanisms involve oxidative stress and apoptosis, but evidence for effective treatments is lacking. To explore the concrete molecular mechanisms of jellyfish toxin-induced cardiotoxicity and to explore effective therapeutic approaches, we established tentacle extract (TE) of jellyfish Nemopilema nomurai induced cardiotoxicity models in vivo and in vitro based Intelligent Character Recognition (ICR) mice and H9C2 cells, respectively,.We assessed toxin-induced cardiac injury and screened antagonists from natural compounds to evaluate their antagonistic effects and explore their mechanisms of action. In vitro experiments showed that TE reduced the viability of H9C2 cells and induced a large number of cells apoptotic, accompanied by the elevation of reactive oxygen species (ROS), malondialdehyde (MDA) and the decrease of total superoxide dismutase (T-SOD), activated the phosphorylation level of mitogen-activated protein kinase (MAPK) nuclear transcription factors p38, extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK), and increased the transcription level of upstream cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), and OMT can significantly antagonize the above changes caused by TE; in vivo experiments demonstrated that TE could lead to the death of mice, as well as induce cardiac edema and rupture of myocardial fibers. In contrast, Oxymatrine (OMT) effectively counteracts the lethal effects of TE and reduces both cardiac edema and myocardial fiber rupture. In summary, OMT can antagonise TE-induced cardiac injury and lethal effects by inhibiting the activation of the MAPK pathway and reducing oxidative stress and apoptosis. As a natural compound, OMT offers a potential therapeutic strategy for jellyfish stings.