Immunosuppressive Sesquiterpene Pyridine Alkaloids from Hook. f.

Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A-J (-), were isolated from the roots of , along with ten known analogues (-). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of , the total alkaloids (TA) and compounds , , and - were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds , , and showed potent immunosuppressive activity, with IC values of 7.25 μg/mL, 8.75 μM, 0.74 μM, and 15.66 μM, respectively, and no influence on the cell viability at a concentration of 100 μg/mL (TA) or 100 μM (, , and ). Accordingly, TA, , , and , especially , were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.