<![CDATA[Background: Hypercholesterolemia is a condition where total cholesterol levels exceed 200 mg/dL, often accompanied by decreased high-density lipoprotein (HDL) levels. This condition increases the risk of cerebrovascular disease, coronary heart disease, and peripheral artery disease. Non-pharmacological interventions using antioxidant-rich Galoba fruit (Hornstedtia sp.) have the potential to improve lipid profiles by modulating cholesterol metabolism. Objective: This study aimed to determine the effect of administering Galoba fruit (Hornstedtia sp.) ethanol extract on HDL-cholesterol levels in mice (Mus musculus) and explore its possible mechanistic pathways. Methods: This laboratory experimental study employed a post-test-only control group design. Twenty-five mice (Mus musculus) were randomly assigned to five groups: normal control (KN), negative control (K−), positive control (K+), treatment dose 1 (D1, 200 mg/kgBW), and treatment dose 2 (D2, 400 mg/kgBW). Hypercholesterolemia was induced through a high-fat diet (quail egg yolk, lard, and used cooking oil). HDL levels were measured after treatment and analyzed using ANOVA followed by a post hoc Tukey HSD test. Results: High-fat diet induction significantly increased total cholesterol levels. Administration of Galoba extract reduced total cholesterol and increased HDL levels. The D1 group (200 mg/kgBW) demonstrated the highest HDL increase of 35.20 mg/dL (81.86%), surpassing D2 (400 mg/kgBW) at 34.80 mg/dL (80.93%). Statistical analysis confirmed a significant increase in HDL levels (ANOVA, p < 0.001), with post hoc Tukey HSD showing significant differences between control and treatment groups. Conclusion: Ethanol extract of Galoba fruit (Hornstedtia sp.) effectively increased HDL levels in hypercholesterolemic mice, with the 200 mg/kgBW dose showing optimal effect. The potential mechanism involves inhibition of the HMG-CoA reductase pathway, which suppresses endogenous cholesterol synthesis, and antioxidant modulation, which reduces oxidative modification of lipoproteins and enhances reverse cholesterol transport. These findings support the therapeutic promise of Hornstedtia sp. as a natural lipid-modulating agent.]]>
