Potential of Red Betel Leaf (Piper ornatum) Extract on Total Cholesterol and Hepatic Histopathology in a Hyperlipidemic Wistar Rat Model

Background: Nonalcoholic fatty liver disease (NAFLD) affects approximately one-third of adults worldwide. However, the effects of Indonesian medicinal plants on its histological components remain insufficiently investigated. Objective: This study evaluated the effects of ethanolic red betel leaf (Piper ornatum) extract on total cholesterol, steatosis, lobular inflammation, and hepatocellular ballooning in hyperlipidemic Wistar rats. Methods: This experimental study used a posttest-only control group design involving 30 male Wistar rats divided into six groups (n = 5): normal control, high-fat diet (HFD) negative control, simvastatin positive control, and extract treatments at 250, 500, and 750 mg/kg body weight. Rats received HFD for 28 days, followed by 28 days of continued HFD with treatment. Cholesterol levels were analyzed using one-way ANOVA and Tukey's test, while histopathological scores were assessed using Kruskal–Wallis and Mann–Whitney U tests. Results: Total cholesterol differed significantly among groups (p = 0.006). Compared with the negative control (94.2 mg/dL), cholesterol levels were significantly lower at 500 mg/kg (p = 0.029) and 750 mg/kg (p = 0.012). Lobular inflammation was also significantly reduced at 500 mg/kg (p = 0.050) and 750 mg/kg (p = 0.031). However, neither steatosis nor hepatocellular ballooning improved significantly. Conclusion: Red betel leaf extract reduced cholesterol levels and lobular inflammation, particularly at higher doses, without significantly improving steatosis or hepatocellular ballooning. These findings suggest predominantly anti-inflammatory effects during the treatment period.