piplartine and Systemic-Inflammatory-Response-Syndrome

Excessive necroptosis contributes to the pathogenesis of several inflammatory and neurodegenerative diseases. Here, using a high-throughput screening approach, we investigated the anti-necroptosis effects of piperlongumine, an alkaloid isolated from the long pepper plant, in vitro and in a mouse model of systemic inflammatory response syndrome (SIRS).. A natural compound library was screened for anti-necroptosis effects in cellular. The underlying mechanism of action of the top candidate piperlongumine was explored by quantifying the necroptosis marker phosphorylated receptor-interacting protein kinase 1 (p-RIPK1) by Western blotting. The anti-inflammatory effect of piperlongumine was assessed in a tumor necrosis factor α (TNFα)-induced SIRS model in mice.. Among the compounds investigated, piperlongumine significantly rescued cell viability. The half maximal effective concentration (EC. As a potent necroptosis inhibitor, piperlongumine prevents phosphorylation of RIPK1 at its activation residue Ser166. Piperlongumine thus potently inhibits necroptosis at concentrations safe enough for human cells in vitro and inhibits TNFα-induced SIRS in mice. Piperlongumine has potential clinical translational value for the treatment of the spectrum of diseases associated with necroptosis, including SIRS.

Topics: Animals; Apoptosis; Humans; Mice; Necrosis; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha