Anti-adipogenic cyathane diterpenoids from Onychium japonicum

Onychium japonicum, a Zhuang ethnic medicine, has demonstrated promising anti-obesity potential in preliminary pharmacological studies. Phytochemical investigation of the whole plant led to the isolation of fifteen cyathane-type diterpenoids, including ten previously undescribed compounds, designated as onyjaponiods A-J (1-10). Notably, compound 1 is the first cyathane diterpenoid with a 3,4-dihydroxybenzaldehyde unit oxygen-bridged between C-7 and C-14. Compounds 2 and 3 feature a rare rearranged 5/6/6-tricyclic cyathane skeleton and represent the second and third examples of this structural class. The planar structures and absolute configurations of all new compounds were unequivocally established through comprehensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and comparative calculated electronic circular dichroism (ECD). Anti-obesity assays showed that compounds 1-15 exerted anti-adipogenic effects in 3T3-L1 adipocytes, with six compounds performing comparably to the positive controls berberine and resveratrol. This study is the first to report the anti-obesity potential of cyathane diterpenoids.