Diterpenoids from the aerial parts of <i>Isodon serra</i> and their anti-hepatocarcinoma potential

Three new <i>ent</i>-kaurane diterpenoids, isodosins E-G (1-3), along with 20 known ones (4-23), were obtained from the aerial parts of <i>Isodon serra</i> (Maxim.) Hara. The structures of the new compounds were elucidated using 1D/2D NMR spectra and HREIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. The <i>in vitro</i> anti-hepatocarcinoma activities of compounds 2, 3, 5, 8, 13, 19, and 23 were evaluated against HepG2 and Huh7 cell lines using the CCK-8 assay. Among them, compounds 3, 8, and 23 exhibited high inhibitory effects on HepG2 cells, with IC₅₀ values of 6.94 ± 9.10 μM, 71.66 ± 10.81 μM, and 43.26 ± 9.07 μM, respectively. In a Hepa1-6 xenograft mouse model, compound 8 significantly inhibited tumor growth at doses of 50 and 100 mg kg^-1, demonstrating its potent anti-hepatocarcinoma activity.