Targeting Reactive Oxygen Species and Inflammation in Sepsis-Induced Liver Injury with Naturally Derived Superoxide Dismutase-Mimicking Carbon Dots

Sepsis-induced liver injury (SILI) is a serious complication of septicemia and contributes to high rates of patient death. SILI is characterized by excessive hepatic reactive oxygen species (ROS) generation, leading to inflammatory response activation and the release of inflammatory mediators that yield liver damage. Efforts to design drugs that can mitigate oxidative stress and inflammatory factor production are thus vital to protecting patients against SILI. Nevertheless, effective pharmacological interventions for SILI therapy are currently absent. Here, natural superoxide dismutase (SOD)-mimetic carbon dots (G-CDs), derived from the traditional medicine plant <i>Glycyrrhiza</i>, with robust ROS-scavenging activity were designed and synthesized as a novel treatment for SILI. These G-CDs possess abundant surface hydroxyl and carbonyl groups such that they can effectively mediate SOD-like enzyme activity exceeding 13,340 U/mg to alleviate ROS overproduction and associated inflammation. In a murine model of lipopolysaccharide-induced SILI, these G-CDs effectively reduced hepatic inflammation, oxidative injury, and tissue damage. From a mechanistic perspective, these G-CDs were found to preserve liver integrity through the activation of Keap1/Nrf2-mediated antioxidant signaling and the inhibition of NF-κB-dependent inflammation, thereby reducing the levels of hepatic inflammation and oxidative stress. In summary, these results highlight the promise of G-CDs as therapeutic candidates capable of treating SILI by mitigating oxidative stress-associated liver injury.