Lingzhiols, Unprecedented Rotary Door-Shaped Meroterpenoids as Potent and Selective Inhibitors of p-Smad3 from Ganoderma lucidum

(+)-Lingzhiol and (-)-lingzhiol, a pair of rotary door-shaped meroterpenoidal enantiomers, were isolated from Ganoderma lucidum. Their structures were identified by spectroscopic methods and X-ray diffraction crystallography. Lingzhiol bears an unusual 5/5/6/6 ring system characteristic of sharing a C-3'-C-7' axis. Biological evaluation showed that (+)-lingzhiol or ()-lingzhiol could selectively inhibit the phosphorylation of Smad3 in TGF-beta 1-induced rat renal proximal tubular cells and activate Nrf2/Keap1 in mesangial cells under diabetic conditions.