Aromatic Norditerpenoids From Blachia pentzii With Anti‐Pulmonary Fibrosis Activity

ABSTRACT Eleven highly oxygenated aromatic norditerpenoids, blapenoids A–K were isolated from the roots of Blachia pentzii , and fully characterized using comprehensive spectroscopic analysis, electronic circular dichroism (ECD), and x‐ray crystallography. Notably, blapenoids A–I feature a densely oxygenated 7,8‐ seco ‐norditerpenoid backbone of the cleistanthane family, branching into the first reported 7,16,17,19,20‐pentanor scaffold (blapenoids A−D), and an unprecedented 16,17,19,20‐tetranor skeleton (blapenoids E–I), for which a plausible biosynthetic pathway was proposed. Intriguingly, chiral‐phase HPLC resolved blapenoids E‐G into enantiopure forms, whereas the structurally analogous blapenoids H and I existed as scalemic mixtures (er 35:1, R / S ). This stereochemical divergence was corroborated by methylation of (+)‐ and (−)‐blapenoid G, followed by LC‐MS analysis. Biological assays revealed that some compounds noncytotoxically inhibited transforming growth factor (TGF‐ β )‐induced fibrogenesis in human lung fibroblasts. Notably, blapenoid K emerged as the most potent (IC 50 = 3.82 µM), dose‐dependently suppressing α ‑smooth muscle actin ( α ‐SMA), fibronectin, and collagen I transcripts, alongside corresponding protein‐level inhibition of α ‐SMA and fibronectin, supporting aromatic norditerpenoids as promising lead compounds for further anti‐pulmonary fibrosis research.