## 3 Results
### DRE Reduces the Liver Weight and Improves the Liver Histology in HFMCD Diet-Induced MASH Model Mice  
To evaluate the protective effects of DRE against MASH, we assessed the liver weight, liver-to-body weight ratio, and histopathological changes in the HFMCD diet-induced MASH model mice. HFMCD diet-fed group exhibited significantly higher absolute liver weight and liver-to-body weight ratio than the ND-fed group, indicating that heptomegaly was associated with steatosis and inflammation. However, DRE significantly reduced liver weight and the liver-to-body weight ratio compared to those in the HFMCD diet-fed group, showing effects comparable to those of quercetin (QUE), an antioxidant flavonoid used as a positive control (Figure 4A,B). Next, histological evaluation of hematoxylin and eosin-stained liver tissues was performed. The ND-fed group showed normal hepatic architecture with no visible lipid accumulation. In contrast, the HFMCD diet-fed group exhibited severe hepatocyte ballooning and excessive accumulation of lipid droplets. Notably, DRE markedly reduced lipid droplet size and accumulation, effectively attenuating hepatic steatosis. Similar histological improvements were observed in the QUE-treated group (Figure 4C).  
Figure 4: Effects of DRE on the liver weight and histological changes in high-fat methionine- and choline-deficient (HFMCD) diet-induced metabolic dysfunction-associated steatohepatitis (MASH)  
Figure 3: Effects of DRE on fibrosis-related gene expression levels in PA-induced AML12 cells. AML12 hepatocytes were treated with PA (0.5 mM) to induce hepatic fibrosis and co-treated with DRE at 50 and 100 \(\upmu\)g/mL. Expression levels of the key fibrotic markers, collagen type I alpha 1 (_COLIA1_), collagen type I alpha 2 (_COLIA2_), and tissue inhibitor of metalloproteinases 1 (_TIMPI_), were assessed via quantitative polymerase chain reaction (qPCR). PA significantly upregulated the _COLIA1_, _COLIA2_, and _TIMPI_ levels compared to those in the control group (* \(p\) < 0.05). However, co-treatment with DRE at 50 and 100 \(\upmu\)g/mL significantly reduced the _COLIA1_ and _COLIA2_ levels in a dose-dependent manner (## \(p\) < 0.01 vs. PA-treated group). Although _TIMPI_ levels were also decreased by DRE, no statistical significance was observed.  
model mice. The mice were fed an HFMCD diet to induce MASH and subsequently treated with DRE or quercetin (QUE, positive control). A normal diet (ND) group was included as a control. (**A**) Liver weight and (**B**) the liver-to-body weight ratio (%) were significantly increased in the HFMCD diet-fed group compared to those in the ND-fed group. However, DRE significantly reduced liver weight and the liver-to-body weight ratio (**\({}^{\star}\)_p_ < 0.01 vs. HFMCD diet-fed group), thereby providing hepatoprotection. (**C**) Representative hematoxylin and eosin (H&E)-stained liver sections (original magnification: \(\times\)200) showing marked hepatic steatosis and ballooning in the HFMCD diet-fed group. DRE markedly reduced the lipid droplet accumulation, similar to QUE. These results suggest that DRE ameliorates hepatic steatosis and liver hypertrophy in MASH.