Picrocylide A: A Cyclobutane-Containing Apocarotenoid-Derived Meroterpenoid from <i>Neopicrorhiza scrophulariiflora</i> with Hepatoprotective Effect

Picrocylide A (<b>1</b>), an apocarotenoid-derived meroterpenoid characterized by a rare 4/9/6 tricyclic skeleton, was isolated from the rhizomes of <i>Neopicrorhiza scrophulariiflora</i>, along with its putative biosynthetic precursor, 14-hydroxyaeginetic acid (<b>2</b>). The structure was elucidated by 1<i>D</i>/2D nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectroscopy. The absolute configuration was determined by experimental and calculated electronic circular dichroism spectra matching and GIAO ¹³C NMR chemical shift calculation coupled with DP4+ probability analysis. A plausible biosynthetic pathway for compound <b>1</b> is also proposed. Additionally, compound <b>1</b> exhibited potent hepatoprotective activity against N-acetyl-<i>p</i>-aminophenol (APAP)-induced HepG2 cell damage with an EC₅₀ value of 10.65 μM.