Lindenane Sesquiterpenoid Hetero‐ or Homo‐Dimers From Sarcandra glabra and Their Anti‐Neuroinflammatory Activities

Eighteen lindenane sesquiterpenoid dimers, including three previously undescribed hetero- or homo-dimers (1-3), were isolated from the whole plant of Sarcandra glabra. Their structures were elucidated by High-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance, quantum chemical calculations, and electronic circular dichroism calculations. Notably, compound 1 is a rare hetero-dimer formed by [4 + 2] cycloaddition of a eudesmane and a lindenane sesquiterpene, via C-15-C-9', C-6-C-8', and C-11-C-7' linkages. Compound 2 features a unique epoxide structural motif. All compounds were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 cells. The inhibitory effects of all isolates on LPS-induced NO production in BV-2 cells were evaluated. Thirteen compounds, excluding 3, 5, 13, 15, and 16, exhibited IC₅₀ values ranging from 0.15 to 6.29 µM. Furthermore, compound 1 dose-dependently inhibited the release of NO in BV-2 cells by suppressing the expression of induced NO synthase, cyclooxygenase-2, and MYD88 proteins.