Abstract
<title>Abstract</title> <p> Sepsis remains a significant healthcare challenge with limited effective treatments. In the present study, we investigated the therapeutic potential of DSP_SK1260, a novel compound with anti-inflammatory properties, in two sepsis models: <italic>E. coli</italic> BL21-induced septic shock and Caecal ligation and puncture (CLP) induced polymicrobial sepsis. In septic shock model, DSP_SK1260 administration before infection reduced proinflammatory cytokines, prevented disseminated intravascular coagulation (DIC), and improved survival rates in mice. Furthermore, when DSP_SK1260 was administered after sepsis induction, it effectively reduced TNF-α levels, improved coagulation parameters, and increased fibrinogen, platelet, and white blood cell counts. Therapeutic DSP_SK1260 treatment also enhanced survival in septic mice. In polymicrobial sepsis model induced by CLP, DSP_SK1260 treatment reduced TNF-α levels and restored lymphocyte, monocyte, and white blood cell numbers, which were depleted in sepsis. Additionally, DSP_SK1260 enhanced function of the liver and kidney, as demonstrated by decreased serum ALT and creatinine levels, and improved liver histopathology. Importantly, therapeutic DSP_SK1260 treatment significantly prolonged survival in mice with polymicrobial sepsis induced by CLP, with a 72% increase over the control group. These findings highlight the therapeutic efficacy of DSP_SK1260 in both septic shock and polymicrobial sepsis models. DSP_SK1260 exhibited potent anti-inflammatory effects, preserved organ function, and improved survival rates. The results suggest that DSP_SK1260 holds promise as a potential treatment for sepsis, offering new avenues for targeted intervention in this life-threatening condition. </p>