Immunomodulatory clerodane diterpenoids from the tuberous roots of Paratinospora sagittata (Oliv.) Wei Wang.

Ten new clerodane diterpenoids, paratinosanoids A-J (1-10), featuring a rare nitrogen-containing derivative (1), along with 13 known analogues (11-23), were isolated from the tuberous roots of Paratinospora sagittata (Oliv.) Wei Wang. The structures of these new compounds, including their absolute configurations, were elucidated by spectroscopic and computational methods, as well as single crystal X-ray diffraction. All the diterpenoids were screened for their impact on the immune cells and selected ones could enhance the cell proliferation of T and B lymphocytes. Compound 4 exhibited the most potent activity and effectively prevented lymphocyte apoptosis. Subsequent investigation revealed that compound 4 not only significantly altered the proportions of various T and B cell subsets, but also downregulated key immune checkpoints, including PD-1 and TIM-3, suggesting its potential value in the development of novel immunotherapies.