Fourteen Undescribed Sesquiterpenoids and Lignans With Potent Anti-Inflammatory and Antioxidant Properties Isolated...

This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC₅₀ = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC₅₀ = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC₅₀ = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC₅₀ = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These findings significantly expand the known chemical diversity of S. oblata Lindl., and highlight sesquiterpenes and lignans from this source as promising scaffolds for developing novel anti-inflammatory and antioxidant agents.