Ligulaplenolides A-S, nineteen undescribed eremophilane-type sesquiterpenoids from Ligularia platyglossa and their...

A phytochemical investigation of the aerial parts of Ligularia platyglossa (Franch.) Hand-Mazz led to the isolation of 19 undescribed eremophilane sesquiterpenoids, ligulaplenolides A-S (1-19), together with 26 sesquiterpenoids (20-45), representing five sesquiterpenoid skeletons. Notably, compounds 1 and 2 feature rare eremophilane frameworks that have seldom been reported in the genus Ligularia. Their structures were established through comprehensive spectroscopic data, including HRESIMS, IR, 1D, and 2D NMR. The absolute configurations were unambiguously determined by single-crystal X-ray diffraction. The anti-inflammatory activities of all isolates were evaluated using LPS-induced RAW264.7 macrophage models. Nine isolates (2, 9, 21, 24, 26, 29, 33, 36, and 42) exhibited pronounced inhibitory effects on LPS-induced nitric oxide (NO) overproduction. Among them, compounds 2 and 9 showed remarkable anti-inflammatory activity with IC₅₀ values of 4.50 μM and 14.09 μM, respectively, outperforming the positive control L-NMMA (IC₅₀ = 18.28 μM). Furthermore, 2 and 9 significantly suppressed the production of key inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), (interleukin-6) IL-6, and interleukin-1β (IL-1β). These two compounds exert their anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) expression to reduce NO production and by suppressing IκB phosphorylation to block NF-κB nuclear translocation and subsequent pro-inflammatory cytokine expression. This study clarifies the anti-inflammatory pharmacodynamic material basis of L. platyglossa and elucidates its underlying mechanism through regulating the NF-κB signaling pathway.