Liguladentatanes A-E, five undescribed highly oxygenated bisabolene-type sesquiterpenoids from Ligularia dentata and...

Ligularia dentata Hara (Asteraceae family) is a traditional Chinese medicinal herb used to alleviate breathing difficulties, promote blood circulation, reduce inflammation and pain, suppress coughs, and clear phlegm. A phytochemical investigation of its aerial parts led to five undescribed and highly oxygenated bisabolane sesquiterpenoids, liguladentatanes A - E (1-5), along with eight known sesquiterpenoids (6-13). Their structures were established through comprehensive spectroscopic data including HRESIMS, IR, 1D, and 2D NMR. All the isolates were evaluated for their in vitro anti-inflammatory activity by measuring their ability to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compounds 3, 5, 6, 7, and 8 showed significant inhibitory activity with IC₅₀ values ranging from 14.99 to 22.25 μM. Notably, compound 7 showed a remarkable anti-inflammatory effect with an IC₅₀ value of 14.99 μM, which outperformed that of the positive control (L-NMMA, IC₅₀: 20.70 μM). Furthermore, 7 significantly suppressed the production of key inflammatory cytokines including TNF-α, IL-6, and IL-1β. To explore the potential mechanism, network pharmacology and structural virtual screening strategies were employed. The finding suggested that these bisabolene-type sesquiterpenoids may exert their anti-inflammatory activity by targeting EGFR and PTGS2. This study not only expands the chemical diversity of L. dentata, but also highlights a promising structural motif for the development of anti-inflammatory agents.