## 1 Introduction  
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), represents a spectrum of hepatic disorders characterized by excessive triglyceride (TG) accumulation in hepatocytes in the absence of significant alcohol consumption. MASLD encompasses simple steatosis, which is generally benign, as well as its progressive form, metabolic dysfunction-associated steatohepatitis (MASH, formerly known as NASH), which is marked by inflammation, hepatocellular injury, and varying degrees of fibrosis.  
In advanced stages, MASH can progress to cirrhosis, liver failure, and hepatocellular carcinoma [1, 2, 3]. Unlike simple steatosis, MASH is pathologically characterized by hepatocyte ballooning, cell death, and infiltration of inflammatory cells [4, 5, 6]. It is estimated that approximately 25% of patients with MASLD develop MASH, and nearly 20% of those with MASH eventually progress to cirrhosis or liver cancer, particularly in the context of obesity.  
In accordance with a recent consensus by international liver disease societies, the term \"non-alcoholic steatohepatitis (NASH)\" has been updated to \"MASH\" to better reflect its metabolic etiology and to reduce the stigma associated with alcohol consumption [7]. This nomenclature shift, along with the proposed transition from NAFLD to MASLD, provides a more inclusive and mechanism-based framework for disease classification, diagnosis, and management.  
The progression to MASH is widely explained by the two-hit hypothesis. The first hit is associated with lipid accumulation, following insulin resistance, obesity, and de novo adipogenesis. The second hit results in fibrosis of the liver tissue and chronic liver injury via oxidative stress, pro-inflammatory cytokine production, and apoptosis [8]. Despite its increasing global prevalence, only limited prevention and treatment options are currently available for MASH.  
Natural product-derived compounds have attracted attention as potential preventive and therapeutic agents owing to their antioxidant, anti-inflammatory, and inhibitory effects on lipid accumulation. Some nutraceuticalals, including silymarin, curcumin, and resveratrol, have shown promising hepatocyte effects against MASH by modulating oxidative stress, inflammation, and lipid metabolism. However, these examples are relatively few, and the discovery of novel natural compounds targeting MASH remains limited, indicating the need for further exploration [9]. _Distylium racemosum_ (_D. racemosum_), an evergreen plant native to Jeju Island, exerts various effects, such as anti-obesity, antioxidant, and anti-inflammatory [10]. However, its hepatoprotective effects and molecular mechanisms against MASH remain unknown.  
Individuals with MASH show a substantially increased likelihood of liver cancer development compared to those with viral hepatitis, particularly in the presence of obesity [11]. This highlights the urgent need for effective treatment methods for MASH. As the _D. racemosum_ ethyl acetate fraction (DRE) exerts anti-obesity effects, its active ingredient possibly protects against MASH.  
In this study, we investigated the effects and action mechanisms of DRE on MASH using hepatocytes and mouse models. We also evaluated the potential of DRE as a MASH prevention and treatment agent by analyzing its key active ingredients via high-performance liquid chromatography (HPLC) analysis.