Dibenzocyclooctadiene lignans from Kadsura coccinea and their immunosuppressive activities

A detailed phytochemical analysis of the dried, ripe fruits of Kadsura coccinea led to the isolation and structural characterization of eleven undescribed lignans, designated kadcolignan K-U (1-11), together with thirteen previously documented compounds (12-24). Notably, kadcolignan U (11) is particularly distinctive, representing a rare dearomatized lignan with a dienone moiety and an uncommon 7, 2'-oxygen bridge. Mechanistic evaluation of the most potent isolates, kadcolignan O (5) and kadcolignan Q (7), revealed their capacity to trigger apoptosis in activated mice B lymphocytes through mitochondrial-dependent pathways, as evidenced by dose-dependent elevation of pro-apoptotic Bax, suppression of anti-apoptotic Bcl-2/Bcl-xL, and release of cleaved caspase-3 and caspase-9. Additionally, both metabolites were found to disrupt the PI3K/AKT/mTOR signaling axis by inhibiting the phosphorylation of PI3K, AKT, and mTOR in a dose-dependent manner. Our findings highlight K. coccinea as a source of B cell-targeted immunosuppressants, with 5 and 7 emerging as promising candidates for further development in autoimmune disease therapy.