Kaempferol in a complex formula protects heart from jellyfish venom by modulating MAPK signaling

Jellyfish stings are a prevalent public health concern in coastal regions worldwide, safe and effective therapeutic strategies remain elusive due to unclear pathogenic mechanisms. In this study, Modified Huanglian Jiedu Decoction (MHJD), a traditional Chinese medicine formula with heat-clearing and detoxifying properties, was selected to investigate the cardioprotective effects and underlying mechanisms of MHJD and its key component kaempferol against cardiac injury induced by Nemopilema nomurai venom (TE), using a combination of in vitro and in vivo experiments, network pharmacology and molecular docking techniques. TE impaired the viability of H9c2 cardiomyocyte, activated the MAPK signaling pathway, exacerbated oxidative stress and upregulated pro-inflammatory cytokine expression, while MHJD ameliorated these toxic effects. Network pharmacology identified kaempferol as the pivotal bioactive component of MHJD, and subsequent experiments confirmed that kaempferol antagonized TE-induced cardiomyocyte cytotoxicity by inhibiting the MAPK signaling pathway. In conclusion, kaempferol is the critical material basis for the cardioprotective effect of MHJD against jellyfish envenomation, and it serves as a promising therapeutic bioactive compound for the treatment of jellyfish envenomation.