Four New Sesquiterpene Pyridine Alkaloids from the Roots of Tripterygium wilfordii Hook. f

Investigation of the roots of <i>Tripterygium wilfordii</i> Hook. f. resulted in the isolation of nine sesquiterpene pyridine alkaloids (SPAs), including four previously undescribed compounds <b>1</b>-<b>4</b>. The structures of all compounds were elucidated by extensive spectroscopic analysis, including NMR and HRESIMS. In particular, compound <b>1</b> was found to possess an unprecedented cage-like ether moiety, representing the first report of such a structural feature within this class of alkaloids. All isolated compounds were evaluated for their anti-inflammatory activity using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. Compounds <b>1</b>, <b>2</b>, and <b>4</b> exhibited significant inhibition of nitric oxide (NO) production, with IC₅₀ values of 7.14 ± 1.89, 8.55 ± 0.37, and 14.76 ± 0.39 μM. Furthermore, compounds <b>1</b> and <b>2</b> suppressed the secretion of key pro-inflammatory cytokines, including TNF-<i>α</i>, IL-6, and IL-1<i>β</i>, in the same cellular model. These results not only enhanced the structural diversity of SPAs identified from <i>T. wilfordii</i>, but also highlight their potential as promising anti-inflammatory lead compounds.