Natural plant-derived superoxide dismutase nanoenzyme for sepsis-induced liver injury therapy.

Sepsis-induced liver injury is an important cause of septicemia deaths, this injury is characterized by an overproduction of reactive oxygen species (ROS) within the liver, which activates the inflammatory response and results in the release of numerous inflammatory factors, ultimately leading to liver damage. Thus, the development of medicines capable of eliminating ROS and reducing inflammatory factors holds significant prospects. In this study, we synthesized and characterized a natural superoxide dismutase-mimicking carbon dots (G-CDs) form a greenery Glycyrrhiza with distinctive ROS scavenging ability for SILI therapy. The abundant surface unsaturated groups especially oxhydry and carbonyl groups enable G-CDs to exhibit excellent SOD-like enzyme activity exceeding 10000 U/mg and significantly reduce the excessive production of ROS and inflammatory factors. In addition, G-CDs reduced inflammation, oxidative damage, and tissue damage in the liver of lipopolysaccharide (LPS) induced SILI mice model. Mechanistically, G-CDs protect liver tissue by activating Keap-1/Nrf-2 mediated antioxidant signaling and inhibiting NF-κB-dependent inflammatory responses. In conclusion, this study establishes the potential of G-CDs as a promising therapeutic agent for the treatment SILI. RAW264.7 cells were cultured in a 6 wells plate in LPS (1 μg/ml) containing medium for 6 h supplemented with or without G-CDs (400 μg/ml), and total RNA was extracted using the TRIzol reagent. RNA sequencing was conducted using the Bioanalyzer 2100 system (Agilent Technologies, CA, USA).

脓毒症诱导肝损伤（Sepsis-induced liver injury, SILI）是脓毒症患者死亡的重要诱因，该损伤以肝脏内活性氧（reactive oxygen species, ROS）过量生成为核心特征，可激活炎症应答并促使大量炎症因子释放，最终引发肝脏损伤。因此，开发能够清除活性氧、降低炎症因子水平的药物具有重要的应用前景。本研究以绿色环保方式从甘草（Glycyrrhiza）中合成并表征了一种模拟超氧化物歧化酶（superoxide dismutase, SOD）的碳点（G-CDs），其具备优异的ROS清除能力，可用于脓毒症诱导肝损伤的治疗。该碳点表面富含不饱和基团，尤其是羟基与羰基，使其展现出超过10000 U/mg的类超氧化物歧化酶活性，可显著减少过量生成的ROS与炎症因子。此外，在脂多糖（lipopolysaccharide, LPS）诱导的脓毒症诱导肝损伤小鼠模型中，G-CDs可有效减轻小鼠肝脏的炎症反应、氧化损伤与组织损伤。从机制层面而言，G-CDs通过激活Kelch样ECH相关蛋白1/核因子红细胞2相关因子2（Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2, Keap-1/Nrf-2）介导的抗氧化信号通路，并抑制核因子κB（nuclear factor kappa-B, NF-κB）依赖的炎症应答，从而保护肝脏组织。综上，本研究证实G-CDs作为一种极具潜力的治疗制剂，可用于脓毒症诱导肝损伤的治疗。本研究开展了体外细胞实验：将RAW264.7细胞（RAW264.7 cells）接种于6孔板中，在含有1 μg/ml脂多糖的培养基中培养6小时，同时添加或不添加400 μg/ml的G-CDs；随后使用TRIzol试剂（TRIzol reagent）提取总RNA，采用生物分析仪2100系统（Bioanalyzer 2100 system，安捷伦科技（Agilent Technologies, CA, USA））进行RNA测序。