Highly oxygenated lanostane triterpenoids from Ganoderma applanatum and their anti-liver fibrosis effects

Inspired by the intriguing structures and significant activities of Ganoderma triterpenoids (GTs), the EtOAc extract of Ganoderma applanatum was phytochemically investigated, leading to the isolation of 11 GTs, including 10 new one (1-10). Their structures including absolute configurations, were elucidated through IR, UV, HRESIMS, 1D NMR and 2D NMR data analyses. Notably, applanoids J (1) and K (2) represent the first example of GTs with an unprecedented B-seco-lanostane architecture featuring 1,4-cyclohexanedione motif. Meanwhile, compounds 1-7 and 9-11 were evaluated for their hepatoprotective activity using TGF-β1-induced liver fibrosis model, and some of them such as compounds 2, 4, 6, 7 and 10 significantly suppressed the abnormal upregulation of fibrosis-related genes FN, ACTA2 (encode α-SMA) and COL1A1. Mechanistic studies suggested that the anti-liver fibrosis effect of compound 7 may be mediated through inhibition of the TGF-β/Smad signaling pathway. This study not only illustrates the structural diversity of GTs but also highlights their potential as promising anti-liver fibrosis agents.