Sesquiterpenoids from Achillea setacea Waldst. & Kit. with anti-inflammatory activity by inhibiting the glycolytic pathway.

Six previously undescribed sesquiterpenoids, named achisetaces A-F (1-6), involving a rare C6-O-C10 bridged guaianolide-type sesquiterpenoid (1), along with nine known analogues (7-15), were obtained from the aerial parts of Achillea setacea Waldst. & Kit. The undescribed structures of 1-6 including their absolute configurations were determined through spectroscopic techniques (IR, UV, HRESIMS, 1D and 2D NMR), combined with DP4+ NMR analysis and quantum electronic circular dichroism (ECD) calculations. The inhibitory effects of compounds 1-15 on nitric oxide (NO) production were evaluated in LPS-induced RAW 264.7 cells. Compounds 6 and 10 exhibited significant anti-inflammatory activities with IC50 values of 1.56 ± 0.32 and 6.89 ± 0.47 μM, respectively. Moreover, a mechanistic study revealed that compound 6 exerted the anti-inflammatory activity by regulating the glycolytic pathway via suppression of PFKFB3 activation.