A pair of coumarin-based polycyclic meroterpenoid enantiomers (+)/(-)-gerbeloid A [(+)- and (-)-] were isolated from the medicinal plant , which have a unique caged oxatricyclo [4.2.2.0] decene scaffold. Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis. Guided by the hypothetical biosynthetic pathway, the biomimetic synthesis of racemic was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material oxa-6 electrocyclization and intramolecular [2 + 2] photocycloaddition. Subsequently, the results of the biological activity assay demonstrated that both (+)- and (-)- exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model. Notably, the lipid-lowering activity of (+)- is better than that of (-)- at the same concentration, and molecular mechanism study has shown that (+)- and (-)- impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBP/PPAR signaling and Perilipin signaling and . Our findings provide a promising drug model molecule for the treatment of obesity.