Bioactive Compounds in <i>Synsepalum dulcificum</i> Daniell (Miracle Fruits) Kernels: Structural Elucidation and Lipid-Lowering Efficacy

This study investigates the lipid-lowering potential of <i>Synsepalum dulcificum</i> Daniell (miracle fruit) kernels using zebrafish models. Bioactivity-guided fractionation identified ethyl acetate (EA) and <i>n-</i>butanol (NB) fractions as significantly reducing the level of lipid accumulation. Phytochemical analysis led to the isolation of nine compounds, including five novel triterpenoid glycosides (<b>1</b>-<b>5</b>) and one new coumaroylethanolamine glycoside (<b>6</b>) from the NB fraction, alongside flavonoids (<b>7</b>-<b>8</b>) and a triterpenoid-coumaroyl conjugate (<b>9</b>) from the EA fraction. Compounds <b>1</b>-<b>5</b> and <b>7</b> demonstrated potent dose-dependent reductions in triglyceride (TG) and total cholesterol (TC) at the phenotypic level. The Q-PCR experiment showed that the active compounds upregulated the expression of <i>PPARγ</i> and <i>AMPKα1</i>, while they downregulated the expression of <i>FAS</i>. Structure-activity relationships indicated glycosylation patterns critically influence efficacy. This study first reports novel triterpenoid glycosides from miracle fruit kernels with significant lipid-lowering activity for functional foods.