Insight of protease and PLA₂ activity co-inhibition on jellyfish toxin-induced inflammation and multiple organ...

In recent years, global climate change has caused fluctuations in the quantity and activity of phospholipase and proteases prevalent in animal venoms, leading to changes in the patterns of toxic animal injuries and increased treatment difficulties. Herein, this study conducted a screening for inhibitors of jellyfish venom enzyme activity and unexpectedly discovered that Salvianolic acid B (SaB) can inhibit the activities of phospholipase A₂ (PLA₂) and proteases in jellyfish venom. Compared to protease inhibitor mixtures, this co-inhibition exhibited a more pronounced protective effect on the hemocyte, with 300 μM SaB reducing the hemolytic activity of jellyfish venom from 85 % to 57 %. In a macrophage envenomation model, SaB restored the altered trends of the key MAPK pathway proteins (ERK, Jun, and p38) and prevented the upregulation of cytokine genes. SaB is not only a co-inhibitor of proteases, PLA₂, and inflammation but also reverses multi-organ dysfunction in envenomated mice, and timely intervention is a crucial therapeutic method. Collectively, the capacity to simultaneously inhibit both PLA₂ and protease activities could be a crucial criterion for therapeutic agents for treating venomous jellyfish stings. This presents a novel therapeutic agent and strategy for the treatment of envenomations.