Anti‑Inflammatory Sesquiterpenoids From Two Asteraceae Plants Native to Kazakhstan: Isolation, Structural Elucidation, and Mechanistic Insights.

Traditionally used in Kazakh folk medicine, the Asteraceae species Taraxacum tianschanicum and Artemisia gracilescens were investigated for their sesquiterpenoid profiles despite being rich in flavonoids and fatty acids, leading to the isolation of 10 sesquiterpenoids of three structural types. These include one previously undescribed germacrane (1) and two known germacranes (2 and 3) from T. tianschanicum, as well as two germacranes (4 and 5), one guaiane (6), and four eudesmanes (7-10) from A. gracilescens. The structures of these compounds were established through comprehensive analysis of the spectroscopic data and electronic circular dichroism (ECD) calculations. Several compounds exhibited significant anti-inflammatory effects (IC50 = 1.15-8.37 µM) with low cytotoxicity, and mechanistic studies on structurally distinct sesquiterpenoids 4 (germacrane-type) and 8 (eudesmane-type) revealed that both suppress IL-6, IL-1β, iNOS, and COX-2. Notably, unlike compound 4, the activity of 8 involved suppression of the MAPK pathway, indicating a clear mechanistic divergence.