Toonasonoids A-K, limonoids from Toona ciliata M. Roem, attenuate inflammatory response through mediating the...

Eleven previously undescribed limonoids, toonasonoids A-K (1-11), and a known semi-synthetic analogue (12) with three basic carbon skeletons, were isolated from the twigs of Toona ciliata M. Roem. Among them, compounds 1-3 possessed a six-membered α,β-unsaturated ketone moiety in ring A, 4-9 characterized with a seven-membered α,β-unsaturated lactone A-ring, and 10-11 featured ring B-seco and formed a B' tetrahydrofuran ring. The relative structures of the undescribed compounds were established via comprehensive spectroscopic analyses and NMR calculation united with DP4+ probability analysis, and their absolute configurations were assigned by ECD calculations. The cytotoxicity, anti-inflammatory, and the action mechanisms of these isolates on the PI3K/AKT/NF-κB signaling pathway were also evaluated. The results demonstrated that compounds 1, 3, 8, and 9 effectively reduced nitric oxide (NO) release with IC₅₀ values ranging from 4.41 to 9.84 μM. Notably, compounds 1 and 9 could inhibit the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), and block NF-κB (p65) nuclear translocation by triggering the PI3K/AKT pathway, indicating their considerable anti-inflammatory effects.