The Nb4C3 MXenzyme Attenuates MASH by Scavenging ROS in a Mouse Model

Shuying He,1,* Yuerong Lv,1,* Zixian Gao,1,* Liang Peng1,2 1Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou city, Guangdong Province, People’s Republic of China; 2Department of Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou city, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Peng, Department of Gastroenterology, Department of Medicine, First Affiliated Hospital of Guangzhou Medical University, No. 151 Yanjiang West Road, Yuexiu District, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel/Fax +862083062090, Email [email protected]: The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing because people’s dietary habits are dominated by high caloric intake and sedentary lifestyles, leading to the accumulation of lipid, reactive oxygen species (ROS) and inflammation. However, treating MASH remains a challenge.Methods: Two-dimensional (2D) niobium carbide (Nb4C3) MXene nanoenzymes (MXenzymes) possess both antioxidant and anti-inflammatory properties and have attracted considerable attention in the tumor and engineering fields. The Nb4C3 MXenzyme was developed for MASH therapy and exhibited biosafety and antilipid peroxidation activity.Results: Nb4C3 reduced excessive ROS and proinflammatory cytokine levels through its antilipid peroxidation activities, resulting in the inhibition of hepatocyte lipid accumulation and inflammation in a methionine–choline-deficient diet (MCD)-induced murine MASH model. Mechanistically, Nb4C3 not only inhibited lipid accumulation and disrupted lipid metabolism in hepatocytes but also attenuated fatty acid-induced cell death by reducing intracellular ROS levels, which significantly promoted the polarization of M1 macrophages to M2 macrophages by alleviating oxidative stress and suppressing inflammatory factor expression.Conclusion: The Nb4C3 MXenzyme can be used as a multifunctional bioactive material to alleviate hepatic steatosis and inflammation in MASH mice through its robust antioxidant and anti-inflammatory activities. Keywords: metabolic dysfunction-associated steatohepatitis, Nb4C3, ROS scavenging, macrophage