Oleanane saponins from Amesiodendron chinense: Dual inhibition of STAT3 and cytokines for immunosuppression.

Phytochemical analysis of Amesiodendron Chinense stems and leaves resulted in the isolation of 26 undescribed oleanane triterpenoid saponins, amesiodendroside A-Z (1-26), using a combination of bioactivity-guided fractionation and global natural products social molecular networking (GNPS). Compounds 1-12 were classified as disaccharides, whereas 13-26 constituted trisaccharides, which are characterized by an arabinose glycosidically linked to the C-3 position of oleanane, with glucose moieties appended to the C-2 and/or C-3 positions of the arabinose. They exhibit diverse acetylation profiles and oxidation state variations at C-16, C-23, and C-28, showing marked correlations between substitution patterns and the typical 1H/13C NMR chemical shifts. Notably, compounds 5, 7, 16, and 25 displayed significant immunosuppressive activities against the proliferation of T and B lymphocytes in vitro, and the preliminary structure-activity relationship was discussed. Furthermore, compounds 7 and 25 exhibited dual immunosuppressive effects by inducing apoptosis in activated T cells through the signal transducer and activator of transcription 3 (STAT3)-mediated mitochondrial pathway and potently suppressing key immunoregulatory cytokines (e.g., IFN-γ, IL-2, and IL-4).