The Nb(4)C(3) MXenzyme Attenuates MASH by Scavenging ROS in a Mouse Model.

OBJECTIVE: 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 (Nb(4)C(3)) MXene nanoenzymes (MXenzymes) possess both antioxidant and anti-inflammatory properties and have attracted considerable attention in the tumor and engineering fields. The Nb(4)C(3) MXenzyme was developed for MASH therapy and exhibited biosafety and antilipid peroxidation activity. RESULTS: Nb(4)C(3) 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, Nb(4)C(3) 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 Nb(4)C(3) 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.