Abstract

Six new diterpenoids, including two verticillane ghardaqenoids A–B (1–2) and four dolabellane ghardaqenoids C–F (3–6), were isolated from the soft coralHeteroxenia ghardaqensiscollected in the South China Sea. The structures of ghardaqenoids A, D, and E (1,4,5) were determined by X-ray diffraction. Ghardaqenoids B, C, and F (2,3,6) were identified on the basis of NMR data, DP4+, and ECD spectral data. In particular, compound6exhibited strong in vitro lipid-lowering activity in free fatty acid (FFA)-induced HepG2 cells and liver organoids. Further mechanistic studies revealed that compound6regulated AMPK-related proteins and genes, thereby inhibiting the accumulation of triglycerides (TG) and total cholesterol (TC). These findings suggested that pharmacological AMPK activation serves as a promising role in lipid-lowering therapeutic strategies.