Structure Characterization of Four New Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii Hook. f. and Anti-Inflammatory Activity Evaluations

Sesquiterpene pyridine alkaloids (SPAs), as a main class of components in <i>Tripterygium wilfordii</i> Hook. f., possess a variety of bioactivities, such as immunosuppressive, insecticidal, and anti-tumor activities. SPAs can be structurally classed into four subtypes: wilfordate-, evoninate-, iso-wilfordate-, and iso-evoninate types. Our previous study unveiled ten new wilfordate-type SPAs, named wilfordatine A-J, isolated from the roots of <i>Tripterygium wilfordii</i> Hook. f., several of which exhibited significant immunosuppressive activities. As an extension and augmentation of the previous findings, we have now isolated one new iso-wilfordate-type SPA, wilfordatine K (<b>1</b>), alongside three new iso-evoninate-type SPAs, wilfordatines L-N (<b>3</b>-<b>5</b>), and six known analogs. Their structures were characterized by the extensive use of 1D and 2D NMR spectroscopic analysis, as well as HRMS data. Interestingly, compounds <b>4</b> and <b>6</b> were found to exhibit potent inhibitory effects on the nuclear factor-kappa B (NF-κB) pathway in lipopolysaccharide (LPS)-induced HEK293/NF-κB-Luc cells, with IC₅₀ values of 1.64 μM and 9.05 μM, respectively. Notably, these two compounds had no influence on the cell viability at a concentration of 100 μM. Consequently, they hold significant promise as potential anti-inflammatory candidates for further exploration and development.